Blouet, Clémence (2006) Dietary protein and the prevention of glycemic dysregulation: effects of glutathione and cysteine intake. PhD thesis Nutrition humaine, UMR Physiologie de la nutrition et du comportement alimentaire, INAPG 2006INAP0020.

Full text available as: - Th‚se_C_Blouet_12112006.pdf ( 5845 Kb )

Licence: Copyright

Abstract

ABSTRACT: Although it has been repeatedly demonstrated that amino acids alter several mechanisms involved in glycemic control, the impact of dietary protein quantity and quality on glucose homeostasis is still a matter of debate. Oxidative stress is acknowledged as an initiating factor in the pathogenesis of insulin resistance, but the effects of cysteine intake, the rate-limiting substrate for glutathione synthesis, on glycemic control has been overlooked.
Following a review of the literature concerning the interactions between protein intake and glycemic control, with a special focus on sulfur amino acids intake, we present the results of our experimental studies conducted in rats. We investigated the effects of high-protein diets on body composition and glycemic control and evaluated the respective contribution of spontaneous decreased energy intake and increased protein intake in these effects. Thereafter, we focused on the effects of an increase in cysteine intake, using a cysteine-rich protein (whey protein enriched with α-lactalbumine) or a cysteine donor (N-acetylcysteine), on glutathione status and glycemic control in rats fed a high-sucrose diet, a model of diet-induced oxidative stress and insulin resistance. Glucose homeostasis was investigated both in the basal state and after several stimulations (meal, oral glucose load or i.v. insulin bolus) and in parallel, several markers of glutathione status, body redox status, nitric oxide production and bioavailability were assessed.
Increasing protein intake reduced adipose tissue deposition and improved glycemic control in healthy rats. In rats fed a high-sucrose diet, a specific increase in cysteine intake improved glutathione status and prevented oxidative stress, alterations in glycemic control and decreased nitric oxide bioavailability. These results suggest that diet-induced mild oxidative stress leads to an increase in sulfur amino acid requirements and that the noncompletion of these extra requirements could favor the onset of metabolic dysregulations.

References

Ahlborg G, Felig P, Hagenfeldt L, Hendler R, Wahren J. (1974) Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids. J Clin
Invest 53:1080-1090.
Aizawa T, Sato Y, Ishihara F, Taguchi N, Komatsu M, Suzuki N, Hashizume K, Yamada T. (1994)
ATP-sensitive K+ channel-independent glucose action in rat pancreatic beta-cell. Am J Physiol
266 :C622-627.
Ammon HP, Hehl KH, Enz G, Setiadi-Ranti A, Verspohl EJ. (1986) Cysteine analogues potentiate glucose-induced insulin release in vitro. Diabetes 35:1390-1396.
Ammon HP, Klumpp S, Fuss A, Verspohl EJ, Jaeschke H, Wendel A, Muller P. (1989) A possible role of plasma glutathione in glucose-mediated insulin secretion: in vitro and in vivo studies in rats.
Diabetologia 32:797-800.
Ammon HP, Muller PH, Eggstein M, Wintermantel C, Aigner B, Safayhi H, Stutzle M, Renn W.
(1992) Increase in glucose consumption by acetylcysteine during hyperglycemic clamp. A study with healthy volunteers. Arzneimittelforschung 42:642-645.
Anderson GH, Tecimer SN, Shah D, Zafar TA. (2004) Protein source, quantity, and time of consumption determine the effect of proteins on short-term food intake in young men. J Nutr
134 :3011-3015.
Anderson ME. (1985) Determination of glutathione and glutathione disulfide in biological samples.
Methods Enzymol 113:548-555.
Armstrong JL, Bonavaud SM, Toole BJ, Yeaman SJ. (2001) Regulation of glycogen synthesis by amino acids in cultured human muscle cells. J Biol Chem 276:952-956.
Arnal MA, Mosoni L, Boirie Y, Houlier ML, Morin L, Verdier E, Ritz P, Antoine JM, Prugnaud J,
Beaufrere B, Mirand PP. (1999) Protein pulse feeding improves protein retention in elderly women.
Am J Clin Nutr 69:1202-1208.
Arrigo AP. (1999) Gene expression and the thiol redox state. Free Radic Biol Med 27:936-944.
Asante-Appiah E, Kennedy BP. (2003) Protein tyrosine phosphatases: the quest for negative regulators of insulin action. Am J Physiol Endocrinol Metab 284:E663-670.
Azzout-Marniche D, Gaudichon C, Blouet C, Bos C, Mathe V, Huneau JF, Tome D. (2006) Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess ? Am J Physiol:
Baba NH, Sawaya S, Torbay N, Habbal Z, Azar S, Hashim SA. (1999) High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects. Int J Obes Relat
Metab Disord 23:1202-1206.
Badaloo A, Reid M, Forrester T, Heird WC, Jahoor F. (2002) Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition. Am J Clin Nutr
76 :646-652.
Bagley PJ, Stipanuk MH. (1995) Rats fed a low protein diet supplemented with sulfur amino acids have increased cysteine dioxygenase activity and increased taurine production in hepatocytes. J Nutr
125 :933-940.
132Baquet A, Hue L, Meijer AJ, van Woerkom GM, Plomp PJ. (1990) Swelling of rat hepatocytes stimulates glycogen synthesis. J Biol Chem 265:955-959.
Barbagallo M, Dominguez LJ, Tagliamonte MR, Resnick LM, Paolisso G. (1999a) Effects of glutathione on red blood cell intracellular magnesium: relation to glucose metabolism. Hypertension
34 :76-82.
Barbagallo M, Dominguez LJ, Tagliamonte MR, Resnick LM, Paolisso G. (1999b) Effects of vitamin
E and glutathione on glucose metabolism: role of magnesium. Hypertension 34:1002-1006.
Baron AD, Tarshoby M, Hook G, Lazaridis EN, Cronin J, Johnson A, Steinberg HO. (2000)
Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle: evidence for capillary recruitment. Diabetes 49:768-774.
Barrett EJ, Gusberg R, Ferrannini E, Tepler J, Felig P, Jacob R, Smith D, DeFronzo RA. (1986)
Amino acid and glucose metabolism in the postabsorptive state and following amino acid ingestion in the dog. Metabolism 35:709-717.
Barrett WC, DeGnore JP, Konig S, Fales HM, Keng YF, Zhang ZY, Yim MB, Chock PB. (1999)
Regulation of PTP1B via glutathionylation of the active site cysteine 215. Biochemistry 38:66996705.Barthel A, Schmoll D. (2003) Novel concepts in insulin regulation of hepatic gluconeogenesis. Am J
Physiol Endocrinol Metab 285:E685-692.
Batterham RL, Heffron H, Kapoor S, Chivers JE, Chandarana K, Herzog H, Le Roux CW, Thomas
EL, Bell JD, Withers DJ. (2006) Critical role for peptide YY in protein-mediated satiation and bodyweight regulation. Cell Metab 4:223-233.
Baum JI, Layman DK, Freund GG, Rahn KA, Nakamura MT, Yudell BE. (2006) A reduced carbohydrate, increased protein diet stabilizes glycemic control and minimizes adipose tissue glucose disposal in rats. J Nutr 136:1855-1861.
Baum JI, O'Connor JC, Seyler JE, Anthony TG, Freund GG, Layman DK. (2005) Leucine reduces the duration of insulin-induced PI 3-kinase activity in rat skeletal muscle. Am J Physiol Endocrinol Metab
288 :E86-91.
Bauman PF, Smith TK, Bray TM. (1988) The effect of dietary protein and sulfur amino acids on hepatic glutathione concentration and glutathione-dependent enzyme activities in the rat. Can J
Physiol Pharmacol 66:1048-1052.
Beaufrère B. (2002) [Amino acid metabolism in normal individuals]. Journ Annu Diabetol Hotel
Dieu:93-103.
Belfiore F. (2000) Insulin sensitivity indexes calculated from oral glucose tolerance test data. Diabetes
Care 23:1595-1596.
Belfiore F, Iannello S, Volpicelli G. (1998) Insulin sensitivity indices calculated from basal and
OGTT-induced insulin, glucose, and FFA levels. Mol Genet Metab 63:134-141.
Bella DL, Hahn C, Stipanuk MH. (1999a) Effects of nonsulfur and sulfur amino acids on the regulation of hepatic enzymes of cysteine metabolism. Am J Physiol 277:E144-153.
Bella DL, Hirschberger LL, Hosokawa Y, Stipanuk MH. (1999b) Mechanisms involved in the regulation of key enzymes of cysteine metabolism in rat liver in vivo. Am J Physiol 276:E326-335.
133Belobrajdic DP, McIntosh GH, Owens JA. (2004) A high-whey-protein diet reduces body weight gain and alters insulin sensitivity relative to red meat in wistar rats. J Nutr 134:1454-1458.
Bensaid A, Tome D, Gietzen D, Even P, Morens C, Gausseres N, Fromentin G. (2002) Protein is more potent than carbohydrate for reducing appetite in rats. Physiol Behav 75:577-582.
Bensaid A, Tome D, L'Heureux-Bouron D, Even P, Gietzen D, Morens C, Gaudichon C, LarueAchagiotis C, Fromentin G. (2003) A high-protein diet enhances satiety without conditioned taste aversion in the rat. Physiol Behav 78:311-320.
Bessesen DH. (2001) The role of carbohydrates in insulin resistance. J Nutr 131:2782S-2786S.
Bezerra RM, Ueno M, Silva MS, Tavares DQ, Carvalho CR, Saad MJ. (2000) A high fructose diet affects the early steps of insulin action in muscle and liver of rats. J Nutr 130:1531-1535.
Blachier F, Leclercq-Meyer V, Marchand J, Woussen-Colle MC, Mathias PC, Sener A, Malaisse WJ.
(1989) Stimulus-secretion coupling of arginine-induced insulin release. Functional response of islets to L-arginine and L-ornithine. Biochim Biophys Acta 1013:144-151.
Blazquez R, Lopez Quijada C. (1970) The effect of a high-protein diet on plasma glucose concentration, insulin sensitivity and plasma insulin in rats. J Endocrinol 46:445-451.
Blom WA, Lluch A, Stafleu A, Vinoy S, Holst JJ, Schaafsma G, Hendriks HF. (2006) Effect of a high-protein breakfast on the postprandial ghrelin response. Am J Clin Nutr 83:211-220.
Blomstrand E, Eliasson J, Karlsson HK, Kohnke R. (2006) Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise. J Nutr 136:269S-273S.
Bode AM, Foster JD, Nordlie RC. (1992) Glyconeogenesis from L-proline involves metabolite inhibition of the glucose-6-phosphatase system. J Biol Chem 267:2860-2863.
Boden G, Ruiz J, Kim CJ, Chen X. (1996) Effects of prolonged glucose infusion on insulin secretion, clearance, and action in normal subjects. Am J Physiol 270:E251-258.
Boden G, Sargrad K, Homko C, Mozzoli M, Stein TP. (2005) Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern
Med 142:403-411.
Boden G, Tappy L. (1990) Effects of amino acids on glucose disposal. Diabetes 39:1079-1084.
Boger RH, Bode-Boger SM, Sydow K, Heistad DD, Lentz SR. (2000) Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia. Arterioscler Thromb Vasc Biol
20 :1557-1564.
Bois-Joyeux B, Chanez M, Azzout B, Peret J. (1986) Studies on the early changes in rat hepatic fructose 2,6-bisphosphate and enzymes in response to a high protein diet. J Nutr 116:446-454.
Bois-Joyeux B, Chanez M, Peret J. (1987) Changes in rat hepatic fructose 2,6-bisphosphate and 6phosphofructo-2-kinase/fructose 2,6-bisphosphatase activity during three days of consumption of a high protein diet or starvation. Diabete Metab 13:543-548.
134Bolea S, Pertusa JA, Martin F, Sanchez-Andres JV, Soria B. (1997) Regulation of pancreatic beta-cell electrical activity and insulin release by physiological amino acid concentrations. Pflugers Arch
433 :699-704.
Bonadonna RC, Saccomani MP, Del Prato S, Bonora E, DeFronzo RA, Cobelli C. (1998) Role of tissue-specific blood flow and tissue recruitment in insulin-mediated glucose uptake of human skeletal muscle. Circulation 98:234-241.
Bonnefont-Rousselot D. (2002) Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab
Care 5:561-568.
Borel MJ, Williams PE, Jabbour K, Levenhagen D, Kaizer E, Flakoll PJ. (1998) Parenteral glutamine infusion alters insulin-mediated glucose metabolism. JPEN J Parenter Enteral Nutr 22:280-285.
Bos C, Metges CC, Gaudichon C, Petzke KJ, Pueyo ME, Morens C, Everwand J, Benamouzig R,
Tome D. (2003) Postprandial kinetics of dietary amino acids are the main determinant of their metabolism after soy or milk protein ingestion in humans. J Nutr 133:1308-1315.
Brand-Miller JC, Colagiuri S, Gan ST. (2000) Insulin sensitivity predicts glycemia after a protein load. Metabolism 49:1-5.
Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA. (2003) A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 88:1617-1623.
Brennan L, Corless M, Hewage C, Malthouse JP, McClenaghan NH, Flatt PR, Newsholme P. (2003)
13 C NMR analysis reveals a link between L-glutamine metabolism, D-glucose metabolism and gamma-glutamyl cycle activity in a clonal pancreatic beta-cell line. Diabetologia 46:1512-1521.
Brownlee M. (2001) Biochemistry and molecular cell biology of diabetic complications. Nature
414 :813-820.
Brozinick JT, Jr., Roberts BR, Dohm GL. (2003) Defective signaling through Akt-2 and -3 but not
Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. Diabetes 52:935941.Buse MG, Biggers JF, Friderici KH, Buse JF. (1972) Oxidation of branched chain amino acids by isolated hearts and diaphragms of the rat. The effect of fatty acids, glucose, and pyruvate respiration. J
Biol Chem 247:8085-8096.
Busserolles J, Rock E, Gueux E, Mazur A, Grolier P, Rayssiguier Y. (2002a) Short-term consumption of a high-sucrose diet has a pro-oxidant effect in rats. Br J Nutr 87:337-342.
Busserolles J, Zimowska W, Rock E, Rayssiguier Y, Mazur A, Gueux E, Grolier P. (2002b) Rats fed a high sucrose diet have altered heart antioxidant enzyme activity and gene expression
Short-term consumption of a high-sucrose diet has a pro-oxidant effect in rats. Life Sci 71:1303-1312.
Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 11:183-190.
Cai J, Sun WM, Lu SC. (1995) Hormonal and cell density regulation of hepatic gammaglutamylcysteine synthetase gene expression. Mol Pharmacol 48:212-218.
135Calbet JA, MacLean DA. (2002) Plasma glucagon and insulin responses depend on the rate of appearance of amino acids after ingestion of different protein solutions in humans. J Nutr 132:21742182.Cardozo AK, Heimberg H, Heremans Y, Leeman R, Kutlu B, Kruhoffer M, Orntoft T, Eizirik DL.
(2001) A comprehensive analysis of cytokine-induced and nuclear factor-kappa B-dependent genes in primary rat pancreatic beta-cells. J Biol Chem 276:48879-48886.
Cavarape A, Feletto F, Mercuri F, Quagliaro L, Daman G, Ceriello A. (2001) High-fructose diet decreases catalase mRNA levels in rat tissues. J Endocrinol Invest 24:838-845.
Ceriello A. (2003) The possible role of postprandial hyperglycaemia in the pathogenesis of diabetic complications. Diabetologia 46 Suppl 1:M9-16.
Ceriello A, Bortolotti N, Crescentini A, Motz E, Lizzio S, Russo A, Ezsol Z, Tonutti L, Taboga C.
(1998) Antioxidant defences are reduced during the oral glucose tolerance test in normal and noninsulindependent diabetic subjects. Eur J Clin Invest 28:329-333.
Ceriello A, Motz E. (2004) Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler
Thromb Vasc Biol 24:816-823.
Ceriello A, Quagliaro L, Catone B, Pascon R, Piazzola M, Bais B, Marra G, Tonutti L, Taboga C,
Motz E. (2002) Role of hyperglycemia in nitrotyrosine postprandial generation. Diabetes Care
25 :1439-1443.
Chang TW, Goldberg AL. (1978) Leucine inhibits oxidation of glucose and pyruvate in skeletal muscles during fasting. J Biol Chem 253:3696-3701.
Channon KM. (2004) Tetrahydrobiopterin: regulator of endothelial nitric oxide synthase in vascular disease. Trends Cardiovasc Med 14:323-327.
Chao CL, Kuo TL, Lee YT. (2000) Effects of methionine-induced hyperhomocysteinemia on endothelium-dependent vasodilation and oxidative status in healthy adults. Circulation 101:485-490.
Clark MG, Wallis MG, Barrett EJ, Vincent MA, Richards SM, Clerk LH, Rattigan S. (2003) Blood flow and muscle metabolism: a focus on insulin action. Am J Physiol Endocrinol Metab 284:E241258.Clark S, Konstantopoulos N. (1993) Sulphydryl agents modulate insulin- and epidermal growth factor
(EGF)-receptor kinase via reaction with intracellular receptor domains: differential effects on basal versus activated receptors. Biochem J 292:217-223.
Coggins M, Lindner J, Rattigan S, Jahn L, Fasy E, Kaul S, Barrett E. (2001) Physiologic hyperinsulinemia enhances human skeletal muscle perfusion by capillary recruitment. Diabetes
50 :2682-2690.
Cotgreave IA, Gerdes RG. (1998) Recent trends in glutathione biochemistry--glutathione-protein interactions: a molecular link between oxidative stress and cell proliferation? Biochem Biophys Res
Commun 242:1-9.
Cresenzi CL, Lee JI, Stipanuk MH. (2003) Cysteine is the metabolic signal responsible for dietary regulation of hepatic cysteine dioxygenase and glutamate cysteine ligase in intact rats. J Nutr
133 :2697-2702.
136Croset M, Rajas F, Zitoun C, Hurot JM, Montano S, Mithieux G. (2001) Rat small intestine is an insulin-sensitive gluconeogenic organ. Diabetes 50:740-746.
Cui R, Iso H, Pi J, Kumagai Y, Yamagishi K, Tanigawa T, Shimamoto T. (2006) Metabolic syndrome and urinary cGMP excretion in general population. Atherosclerosis:
Cushman SW, Wardzala LJ. (1980) Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J Biol Chem 255:4758-4762.
Czech MP, Lawrence JC, Jr., Lynn WS. (1974a) Evidence for the involvement of sulfhydryl oxidation in the regulation of fat cell hexose transport by insulin. Proc Natl Acad Sci U S A 71:4173-4177.
Czech MP, Lawrence JC, Jr., Lynn WS. (1974b) Hexose transport in isolated brown fat cells. A model system for investigating insulin action on membrane transport. J Biol Chem 249:5421-5427.
Daly M. (2003) Sugars, insulin sensitivity, and the postprandial state. Am J Clin Nutr 78:865S-872S.
Dangin M, Boirie Y, Garcia-Rodenas C, Gachon P, Fauquant J, Callier P, Ballevre O, Beaufrere B.
(2001) The digestion rate of protein is an independent regulating factor of postprandial protein retention. Am J Physiol Endocrinol Metab 280:E340-348.
Darmaun D, Smith SD, Sweeten S, Sager BK, Welch S, Mauras N. (2005) Evidence for accelerated rates of glutathione utilization and glutathione depletion in adolescents with poorly controlled type 1
diabetes. Diabetes 54:190-196.
De Mattia G, Bravi MC, Laurenti O, Cassone-Faldetta M, Armiento A, Ferri C, Balsano F. (1998)
Influence of reduced glutathione infusion on glucose metabolism in patients with non-insulindependent diabetes mellitus. Metabolism 47:993-997.
Del Guerra S, Lupi R, Marselli L, Masini M, Bugliani M, Sbrana S, Torri S, Pollera M, Boggi U,
Mosca F, Del Prato S, Marchetti P. (2005) Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 54:727-735.
Dentin R, Pegorier JP, Benhamed F, Foufelle F, Ferre P, Fauveau V, Magnuson MA, Girard J, Postic
C. (2004) Hepatic glucokinase is required for the synergistic action of ChREBP and SREBP-1c on glycolytic and lipogenic gene expression. J Biol Chem 279:20314-20326.
Di Buono M, Wykes LJ, Cole DE, Ball RO, Pencharz PB. (2003) Regulation of sulfur amino acid metabolism in men in response to changes in sulfur amino acid intakes. J Nutr 133:733-739.
Dickinson DA, Levonen AL, Moellering DR, Arnold EK, Zhang H, Darley-Usmar VM, Forman HJ.
(2004) Human glutamate cysteine ligase gene regulation through the electrophile response element.
Free Radic Biol Med 37:1152-1159.
Diniz YS, Rocha KK, Souza GA, Galhardi CM, Ebaid GM, Rodrigues HG, Novelli Filho JL, Cicogna
AC, Novelli EL. (2006) Effects of N-acetylcysteine on sucrose-rich diet-induced hyperglycaemia, dyslipidemia and oxidative stress in rats. Eur J Pharmacol 543:151-157.
Doi M, Yamaoka I, Fukunaga T, Nakayama M. (2003) Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes. Biochem Biophys Res Commun 312:11111117.137Doi M, Yamaoka I, Nakayama M, Mochizuki S, Sugahara K, Yoshizawa F. (2005) Isoleucine, a blood glucose-lowering amino acid, increases glucose uptake in rat skeletal muscle in the absence of increases in AMP-activated protein kinase activity. J Nutr 135:2103-2108.
Dominy JE, Jr., Hirschberger LL, Coloso RM, Stipanuk MH. (2006) Regulation of cysteine dioxygenase degradation is mediated by intracellular cysteine levels and the ubiquitin-26 S proteasome system in the living rat. Biochem J 394:267-273.
Droge W. (2005) Oxidative enhancement of insulin receptor signaling: experimental findings and clinical implications. Antioxid Redox Signal 7:1071-1077.
Drucker DJ. (2006) The biology of incretin hormones. Cell Metab 3:153-165.
Du XL, Edelstein D, Dimmeler S, Ju Q, Sui C, Brownlee M. (2001) Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest
108 :1341-1348.
Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, Brownlee M. (2000)
Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl
Acad Sci U S A 97:12222-12226.
Dudek SM, Semenkovich CF. (1995) Essential amino acids regulate fatty acid synthase expression through an uncharged transfer RNA-dependent mechanism. J Biol Chem 270:29323-29329.
Duplain H, Burcelin R, Sartori C, Cook S, Egli M, Lepori M, Vollenweider P, Pedrazzini T, Nicod P,
Thorens B, Scherrer U. (2001) Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation 104:342-345.
Edgerton DS, Cardin S, Emshwiller M, Neal D, Chandramouli V, Schumann WC, Landau BR,
Rossetti L, Cherrington AD. (2001) Small increases in insulin inhibit hepatic glucose production solely caused by an effect on glycogen metabolism. Diabetes 50:1872-1882.
Eisenstein AB, Strack I, Gallo-Torres H, Georgiadis A, Miller ON. (1979) Increased glucagon secretion in protein-fed rats: lack of relationship to plasma amino acids. Am J Physiol 236:E20-27.
El Midaoui A, Wu R, de Champlain J. (2002) Prevention of hypertension, hyperglycemia and vascular oxidative stress by aspirin treatment in chronically glucose-fed rats. J Hypertens 20:1407-1412.
Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A,
Giugliano D. (2002) Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 106:2067-2072.
Evans JL, Goldfine ID, Maddux BA, Grodsky GM. (2003) Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 52:1-8.
Fafournoux P, Remesy C, Demigne C. (1982) Stimulation of amino acid transport into liver cells from rats adapted to a high-protein diet. Biochem J 206:13-18.
Faipoux R, Tome D, Bensaid A, Morens C, Oriol E, Bonnano LM, Fromentin G. (2006) Yeast proteins enhance satiety in rats. J Nutr 136:2350-2356.
Farnsworth E, Luscombe ND, Noakes M, Wittert G, Argyiou E, Clifton PM. (2003) Effect of a highprotein, energy-restricted diet on body composition, glycemic control, and lipid concentrations in overweight and obese hyperinsulinemic men and women. Am J Clin Nutr 78:31-39.
138Faure P, Rossini E, Lafond JL, Richard MJ, Favier A, Halimi S. (1997) Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets. J Nutr 127:103107.Federici M, Menghini R, Mauriello A, Hribal ML, Ferrelli F, Lauro D, Sbraccia P, Spagnoli LG, Sesti
G, Lauro R. (2002) Insulin-dependent activation of endothelial nitric oxide synthase is impaired by Olinked glycosylation modification of signaling proteins in human coronary endothelial cells.
Circulation 106:466-472.
Ferrannini E, DeFronzo RA, Gusberg R, Tepler J, Jacob R, Aaron M, Smith D, Barrett EJ. (1988)
Splanchnic amino acid and glucose metabolism during amino acid infusion in dogs. Diabetes 37:237245.Fieseler P, Bridenbaugh S, Nustede R, Martell J, Orskov C, Holst JJ, Nauck MA. (1995)
Physiological augmentation of amino acid-induced insulin secretion by GIP and GLP-I but not by
CCK-8. Am J Physiol 268:E949-955.
Finkelstein JD, Martin JJ, Harris BJ. (1988) Methionine metabolism in mammals. The methioninesparing effect of cystine. J Biol Chem 263:11750-11754.
Flakoll PJ, Kulaylat M, Frexes-Steed M, Hill JO, Abumrad NN. (1991) Amino acids enhance insulin resistance to exogenous glucose infusion in overnight-fasted humans. JPEN J Parenter Enteral Nutr
15 :123-127.
Flakoll PJ, Wentzel LS, Rice DE, Hill JO, Abumrad NN. (1992) Short-term regulation of insulinmediated glucose utilization in four-day fasted human volunteers: role of amino acid availability.
Diabetologia 35:357-366.
Floyd JC, Jr., Fajans SS, Conn JW, Knopf RF, Rull J. (1966a) Insulin secretion in response to protein ingestion. J Clin Invest 45:1479-1486.
Floyd JC, Jr., Fajans SS, Conn JW, Knopf RF, Rull J. (1966b) Stimulation of insulin secretion by amino acids. J Clin Invest 45:1487-1502.
Foretz M, Guichard C, Ferre P, Foufelle F. (1999) Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes. Proc Natl Acad Sci U S A 96:12737-12742.
Forslund AH, Hambraeus L, van Beurden H, Holmback U, El-Khoury AE, Hjorth G, Olsson R,
Stridsberg M, Wide L, Akerfeldt T, Regan M, Young VR. (2000) Inverse relationship between protein intake and plasma free amino acids in healthy men at physical exercise. Am J Physiol Endocrinol
Metab 278:E857-867.
Foster MW, McMahon TJ, Stamler JS. (2003) S-nitrosylation in health and disease. Trends Mol Med
9 :160-168.
Frank GD, Eguchi S, Motley ED. (2005) The role of reactive oxygen species in insulin signaling in the vasculature. Antioxid Redox Signal 7:1053-1061.
Frid AH, Nilsson M, Holst JJ, Bjorck IM. (2005) Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am J Clin Nutr 82:6975.139Fridlyand LE, Philipson LH. (2004) Does the glucose-dependent insulin secretion mechanism itself cause oxidative stress in pancreatic beta-cells? Diabetes 53:1942-1948.
Frisbee JC, Stepp DW. (2001) Impaired NO-dependent dilation of skeletal muscle arterioles in hypertensive diabetic obese Zucker rats. Am J Physiol Heart Circ Physiol 281:H1304-1311.
Fukagawa NK. (2006) Sparing of methionine requirements: evaluation of human data takes sulfur amino acids beyond protein. J Nutr 136:1676S-1681S.
Fukagawa NK, Ajami AM, Young VR. (1996) Plasma methionine and cysteine kinetics in response to an intravenous glutathione infusion in adult humans. Am J Physiol 270:E209-214.
Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, Lanzone A. (2002) N-acetylcysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil
Steril 77:1128-1135.
Gameiro A, Reimann F, Habib AM, O'Malley D, Williams L, Simpson AK, Gribble FM. (2005) The neurotransmitters glycine and GABA stimulate glucagon-like peptide-1 release from the GLUTag cell line. J Physiol 569:761-772.
Ganafa AA, Socci RR, Eatman D, Silvestrova N, Abukhalaf IK, Bayorh MA. (2002) Acute inhibition of glutathione biosynthesis alters endothelial function and blood pressure in rats. Eur J Pharmacol
454 :217-223.
Gannon MC, Nuttall FQ. (2004) Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. Diabetes 53:2375-2382.
Gannon MC, Nuttall FQ, Lane JT, Burmeister LA. (1992) Metabolic response to cottage cheese or egg white protein, with or without glucose, in type II diabetic subjects. Metabolism 41:1137-1145.
Gannon MC, Nuttall FQ, Saeed A, Jordan K, Hoover H. (2003) An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes. Am J Clin Nutr 78:734-741.
Gannon MC, Nuttall JA, Damberg G, Gupta V, Nuttall FQ. (2001) Effect of protein ingestion on the glucose appearance rate in people with type 2 diabetes. J Clin Endocrinol Metab 86:1040-1047.
Gannon MC, Nuttall JA, Nuttall FQ. (2002a) The metabolic response to ingested glycine. Am J Clin
Nutr 76:1302-1307.
Gannon MC, Nuttall JA, Nuttall FQ. (2002b) Oral arginine does not stimulate an increase in insulin concentration but delays glucose disposal. Am J Clin Nutr 76:1016-1022.
Gao ZY, Li G, Najafi H, Wolf BA, Matschinsky FM. (1999) Glucose regulation of glutaminolysis and its role in insulin secretion. Diabetes 48:1535-1542.
Gaudichon C, Mahe S, Benamouzig R, Luengo C, Fouillet H, Dare S, Van Oycke M, Ferriere F,
Rautureau J, Tome D. (1999) Net postprandial utilization of [15N]-labeled milk protein nitrogen is influenced by diet composition in humans. J Nutr 129:890-895.
Gautier JF, Fetita S, Sobngwi E, Salaun-Martin C. (2005) Biological actions of the incretins GIP and
GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes Metab 31:233-242.
Gilon P, Ravier MA, Jonas JC, Henquin JC. (2002) Control mechanisms of the oscillations of insulin secretion in vitro and in vivo. Diabetes 51 Suppl 1:S144-151.
140Giugliano D, Marfella R, Coppola L, Verrazzo G, Acampora R, Giunta R, Nappo F, Lucarelli C,
D'Onofrio F. (1997) Vascular effects of acute hyperglycemia in humans are reversed by L-arginine.
Evidence for reduced availability of nitric oxide during hyperglycemia. Circulation 95:1783-1790.
Godsland IF, Jeffs JA, Johnston DG. (2004) Loss of beta cell function as fasting glucose increases in the non-diabetic range. Diabetologia 47:1157-1166.
Goldfine AB, Beckman JA, Betensky RA, Devlin H, Hurley S, Varo N, Schonbeck U, Patti ME,
Creager MA. (2006) Family history of diabetes is a major determinant of endothelial function. J Am
Coll Cardiol 47:2456-2461.
Goldstein BJ, Mahadev K, Wu X. (2005) Redox paradox: insulin action is facilitated by insulinstimulated reactive oxygen species with multiple potential signaling targets. Diabetes 54:311-321.
Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL. (1999) Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 48:839-847.
Gopaul NK, Manraj MD, Hebe A, Lee Kwai Yan S, Johnston A, Carrier MJ, Anggard EE. (2001)
Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism. Diabetologia 44:706-712.
Gosmain Y, Dif N, Berbe V, Loizon E, Rieusset J, Vidal H, Lefai E. (2005) Regulation of SREBP-1
expression and transcriptional action on HKII and FAS genes during fasting and refeeding in rat tissues. J Lipid Res 46:697-705.
Greiwe JS, Kwon G, McDaniel ML, Semenkovich CF. (2001) Leucine and insulin activate p70 S6
kinase through different pathways in human skeletal muscle. Am J Physiol Endocrinol Metab
281 :E466-471.
Griffith OW. (1999) Biologic and pharmacologic regulation of mammalian glutathione synthesis.
Free Radic Biol Med 27:922-935.
Griffith OW, Bridges RJ, Meister A. (1979a) Transport of gamma-glutamyl amino acids: role of glutathione and gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A 76:6319-6322.
Griffith OW, Meister A. (1979b) Glutathione: interorgan translocation, turnover, and metabolism.
Proc Natl Acad Sci U S A 76:5606-5610.
Gromada J, Rorsman P. (2004) New insights into the regulation of glucagon secretion by glucagonlike peptide-1. Horm Metab Res 36:822-829.
Gual P, Le Marchand-Brustel Y, Tanti JF. (2005) Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochimie 87:99-109.
Guarino MP, Afonso RA, Raimundo N, Raposo JF, Macedo MP. (2003) Hepatic glutathione and nitric oxide are critical for hepatic insulin-sensitizing substance action. Am J Physiol Gastrointest
Liver Physiol 284:G588-594.
Guarino MP, Correia NC, Lautt WW, Macedo MP. (2004) Insulin sensitivity is mediated by the activation of the ACh/NO/cGMP pathway in rat liver. Am J Physiol Gastrointest Liver Physiol
287 :G527-532.
Guarino MP, Macedo MP. (2006) Co-administration of glutathione and nitric oxide enhances insulin sensitivity in Wistar rats. Br J Pharmacol 147:959-965.
141Gustafson LA, Neeft M, Reijngoud DJ, Kuipers F, Sauerwein HP, Romijn JA, Herling AW, Burger
HJ, Meijer AJ. (2001) Fatty acid and amino acid modulation of glucose cycling in isolated rat hepatocytes. Biochem J 358:665-671.
Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R, Channon KM. (2002)
Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of
NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105:1656-1662.
Haber CA, Lam TK, Yu Z, Gupta N, Goh T, Bogdanovic E, Giacca A, Fantus IG. (2003) Nacetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress. Am J Physiol Endocrinol Metab 285:E744-753.
Haesler E, Schneiter P, Temler E, Jequier E, Tappy L. (1994) Effects of infused amino acids and lipids on glucose metabolism in healthy lean humans. Int J Obes Relat Metab Disord 18:307-312.
Hall WL, Millward DJ, Long SJ, Morgan LM. (2003) Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr 89:239-248.
Han D, Handelman G, Marcocci L, Sen CK, Roy S, Kobuchi H, Tritschler HJ, Flohe L, Packer L.
(1997) Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 6:321-338.
Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K.
(2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110:177189.Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. (1998) Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol
Chem 273:14484-14494.
Harber MP, Schenk S, Barkan AL, Horowitz JF. (2005) Effects of dietary carbohydrate restriction with high protein intake on protein metabolism and the somatotropic axis. J Clin Endocrinol Metab
90 :5175-5181.
Haruta T, Uno T, Kawahara J, Takano A, Egawa K, Sharma PM, Olefsky JM, Kobayashi M. (2000) A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol Endocrinol 14:783-794.
Heffetz D, Rutter WJ, Zick Y. (1992) The insulinomimetic agents H2O2 and vanadate stimulate tyrosine phosphorylation of potential target proteins for the insulin receptor kinase in intact cells.
Biochem J 288:631-635.
Hellerstein MK, Neese RA, Linfoot P, Christiansen M, Turner S, Letscher A. (1997) Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. J Clin
Invest 100:1305-1319.
Hellman B, Sehlin J, Taljedal I. (1971) Uptake of alanine, arginine and leucine by mammalian pancreatic beta-cells. Endocrinology 89:1432-1439.
Henriksen EJ, Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ. (1997) Stimulation by alpha-lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats. Life Sci
61 :805-812.
142Hildebrandt W, Hamann A, Krakowski-Roosen H, Kinscherf R, Dugi K, Sauer R, Lacher S, Nobel N,
Bodens A, Bellou V, Edler L, Nawroth P, Droge W. (2004) Effect of thiol antioxidant on body fat and insulin reactivity. J Mol Med 82:336-344.
Hinault C, Mothe-Satney I, Gautier N, Lawrence JC, Jr., Van Obberghen E. (2004) Amino acids and leucine allow insulin activation of the PKB/mTOR pathway in normal adipocytes treated with wortmannin and in adipocytes from db/db mice. Faseb J 18:1894-1896.
Hinault C, Mothe-Satney I, Gautier N, Van Obberghen E. (2006) Amino acids require glucose to enhance, through phosphoinositide-dependent protein kinase 1, the insulin-activated protein kinase B cascade in insulin-resistant rat adipocytes. Diabetologia:
Hirsch S, Ronco AM, Vasquez M, de la Maza MP, Garrido A, Barrera G, Gattas V, Glasinovic A,
Leiva L, Bunout D. (2004) Hyperhomocysteinemia in healthy young men and elderly men with normal serum folate concentration is not associated with poor vascular reactivity or oxidative stress. J
Nutr 134:1832-1835.
Hoppe C, Molgaard C, Vaag A, Barkholt V, Michaelsen KF. (2005) High intakes of milk, but not meat, increase s-insulin and insulin resistance in 8-year-old boys. Eur J Clin Nutr 59:393-398.
Hoy M, Maechler P, Efanov AM, Wollheim CB, Berggren PO, Gromada J. (2002) Increase in cellular glutamate levels stimulates exocytosis in pancreatic beta-cells. FEBS Lett 531:199-203.
Huang CS, Chang LS, Anderson ME, Meister A. (1993) Catalytic and regulatory properties of the heavy subunit of rat kidney gamma-glutamylcysteine synthetase. J Biol Chem 268:19675-19680.
Hum S, Koski KG, Hoffer LJ. (1992) Varied protein intake alters glutathione metabolism in rats. J
Nutr 122:2010-2018.
Iiboshi Y, Papst PJ, Kawasome H, Hosoi H, Abraham RT, Houghton PJ, Terada N. (1999) Amino acid-dependent control of p70(s6k). Involvement of tRNA aminoacylation in the regulation. J Biol
Chem 274:1092-1099.
Iritani N, Sugimoto T, Fukuda H, Komiya M, Ikeda H. (1997) Dietary soybean protein increases insulin receptor gene expression in Wistar fatty rats when dietary polyunsaturated fatty acid level is low. J Nutr 127:1077-1083.
Ishihara H, Maechler P, Gjinovci A, Herrera PL, Wollheim CB. (2003) Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells. Nat Cell Biol 5:330-335.
Iwashita S, Mikus C, Baier S, Flakoll PJ. (2006) Glutamine supplementation increases postprandial energy expenditure and fat oxidation in humans. JPEN J Parenter Enteral Nutr 30:76-80.
Jackson AA, Gibson NR, Lu Y, Jahoor F. (2004) Synthesis of erythrocyte glutathione in healthy adults consuming the safe amount of dietary protein. Am J Clin Nutr 80:101-107.
Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K.
(1999) Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol Med 27:309-314.
Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ, Dietze GJ, Henriksen EJ. (1996) The antioxidant alpha-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscle. Diabetes 45:1024-1029.
143Jacqueminet S, Briaud I, Rouault C, Reach G, Poitout V. (2000) Inhibition of insulin gene expression by long-term exposure of pancreatic beta cells to palmitate is dependent on the presence of a stimulatory glucose concentration. Metabolism 49:532-536.
Jahoor F, Jackson A, Gazzard B, Philips G, Sharpstone D, Frazer ME, Heird W. (1999) Erythrocyte glutathione deficiency in symptom-free HIV infection is associated with decreased synthesis rate. Am
J Physiol 276:E205-211.
Jahoor F, Peters EJ, Wolfe RR. (1990) The relationship between gluconeogenic substrate supply and glucose production in humans. Am J Physiol 258:E288-296.
Jean C, Rome S, Mathe V, Huneau JF, Aattouri N, Fromentin G, Achagiotis CL, Tome D. (2001)
Metabolic evidence for adaptation to a high protein diet in rats. J Nutr 131:91-98.
Jiang G, Zhang BB. (2003) Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol
Metab 284:E671-678.
Johnston CS, Day CS, Swan PD. (2002) Postprandial thermogenesis is increased 100% on a highprotein, low-fat diet versus a high-carbohydrate, low-fat diet in healthy, young women. J Am Coll
Nutr 21:55-61.
Jourd'heuil D, Hallen K, Feelisch M, Grisham MB. (2000) Dynamic state of S-nitrosothiols in human plasma and whole blood. Free Radic Biol Med 28:409-417.
Jungas RL, Halperin ML, Brosnan JT. (1992) Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans. Physiol Rev 72:419-448.
Kabir M, Rizkalla SW, Quignard-Boulange A, Guerre-Millo M, Boillot J, Ardouin B, Luo J, Slama G.
(1998) A high glycemic index starch diet affects lipid storage-related enzymes in normal and to a lesser extent in diabetic rats. J Nutr 128:1878-1883.
Kadiiska MB, Gladen BC, Baird DD, Germolec D, Graham LB, Parker CE, Nyska A, Wachsman JT,
Ames BN, Basu S, Brot N, Fitzgerald GA, Floyd RA, George M, Heinecke JW, Hatch GE, Hensley
K, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts LJ, 2nd, Rokach J,
Shigenaga MK, Sohal RS, Sun J, Tice RR, Van Thiel DH, Wellner D, Walter PB, Tomer KB, Mason
RP, Barrett JC. (2005) Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Radic Biol Med 38:698-710.
Kaloyianni M, Freedland RA. (1990) Contribution of several amino acids and lactate to gluconeogenesis in hepatocytes isolated from rats fed various diets. J Nutr 120:116-122.
Kaneto H, Kajimoto Y, Miyagawa J, Matsuoka T, Fujitani Y, Umayahara Y, Hanafusa T, Matsuzawa
Y, Yamasaki Y, Hori M. (1999) Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 48:2398-2406.
Karabatas LM, De Bruno LF, Pastorale C, Lombardo YB, Basabe JC. (2000) Branched-chain amino acid-enriched diet: effects on insulin secretion and cellular immune aggression. Proc Soc Exp Biol
Med 224:159-165.
Kawasaki T, Kashiwabara A, Sakai T, Igarashi K, Ogata N, Watanabe H, Ichiyanagi K, Yamanouchi
T. (2005) Long-term sucrose-drinking causes increased body weight and glucose intolerance in normal male rats. Br J Nutr 93:613-618.
Kettelhut IC, Foss MC, Migliorini RH. (1980) Glucose homeostasis in a carnivorous animal (cat) and in rats fed a high-protein diet. Am J Physiol 239:R437-444.
144Khamaisi M, Kavel O, Rosenstock M, Porat M, Yuli M, Kaiser N, Rudich A. (2000) Effect of inhibition of glutathione synthesis on insulin action: in vivo and in vitro studies using buthionine sulfoximine. Biochem J 349:579-586.
Khan MA, Gannon MC, Nuttall FQ. (1992) Glucose appearance rate following protein ingestion in normal subjects. J Am Coll Nutr 11:701-706.
Kim JK, Fillmore JJ, Sunshine MJ, Albrecht B, Higashimori T, Kim DW, Liu ZX, Soos TJ, Cline
GW, O'Brien WR, Littman DR, Shulman GI. (2004a) PKC-theta knockout mice are protected from fat-induced insulin resistance. J Clin Invest 114:823-827.
Kim SK, Woodcroft KJ, Khodadadeh SS, Novak RF. (2004b) Insulin signaling regulates gammaglutamylcysteine ligase catalytic subunit expression in primary cultured rat hepatocytes. J Pharmacol
Exp Ther 311:99-108.
Kim YB, Kotani K, Ciaraldi TP, Henry RR, Kahn BB. (2003) Insulin-stimulated protein kinase C lambda/zeta activity is reduced in skeletal muscle of humans with obesity and type 2 diabetes: reversal with weight reduction. Diabetes 52:1935-1942.
Kitabchi AE, Temprosa M, Knowler WC, Kahn SE, Fowler SE, Haffner SM, Andres R, Saudek C,
Edelstein SL, Arakaki R, Murphy MB, Shamoon H. (2005) Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin. Diabetes 54:2404-2414.
Klatt P, Lamas S. (2000) Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem 267:4928-4944.
Klatt P, Molina EP, De Lacoba MG, Padilla CA, Martinez-Galesteo E, Barcena JA, Lamas S. (1999)
Redox regulation of c-Jun DNA binding by reversible S-glutathiolation. Faseb J 13:1481-1490.
Klaus S. (2005) Increasing the protein:carbohydrate ratio in a high-fat diet delays the development of adiposity and improves glucose homeostasis in mice. J Nutr 135:1854-1858.
Kohli R, Meininger CJ, Haynes TE, Yan W, Self JT, Wu G. (2004) Dietary L-arginine supplementation enhances endothelial nitric oxide synthesis in streptozotocin-induced diabetic rats. J
Nutr 134:600-608.
Konukoglu D, Hatemi H, Ozer EM, Gonen S, Akcay T. (1997) The erythrocyte glutathione levels during oral glucose tolerance test. J Endocrinol Invest 20:471-475.
Koska J, Blazicek P, Marko M, Grna JD, Kvetnansky R, Vigas M. (2000) Insulin, catecholamines, glucose and antioxidant enzymes in oxidative damage during different loads in healthy humans.
Physiol Res 49 Suppl 1:S95-100.
Krauss S, Zhang CY, Scorrano L, Dalgaard LT, St-Pierre J, Grey ST, Lowell BB. (2003) Superoxidemediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest
112 :1831-1842.
Krebs M, Brehm A, Krssak M, Anderwald C, Bernroider E, Nowotny P, Roth E, Chandramouli V,
Landau BR, Waldhausl W, Roden M. (2003) Direct and indirect effects of amino acids on hepatic glucose metabolism in humans. Diabetologia 46:917-925.
145Krebs M, Krssak M, Bernroider E, Anderwald C, Brehm A, Meyerspeer M, Nowotny P, Roth E,
Waldhausl W, Roden M. (2002) Mechanism of amino acid-induced skeletal muscle insulin resistance in humans. Diabetes 51:599-605.
Krieger-Brauer HI, Kather H. (1992) Human fat cells possess a plasma membrane-bound H2O2generating system that is activated by insulin via a mechanism bypassing the receptor kinase. J Clin
Invest 89:1006-1013.
Kuboki K, Jiang ZY, Takahara N, Ha SW, Igarashi M, Yamauchi T, Feener EP, Herbert TP, Rhodes
CJ, King GL. (2000) Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation 101:676-681.
Kurpad AV, Regan MM, Varalakshmi S, Gnanou J, Young VR. (2004) Daily requirement for total sulfur amino acids of chronically undernourished Indian men. Am J Clin Nutr 80:95-100.
Lacroix M, Gaudichon C, Martin A, Morens C, Mathe V, Tome D, Huneau JF. (2004) A long-term high-protein diet markedly reduces adipose tissue without major side-effects in Wistar male rats. Am J
Physiol Regul Integr Comp Physiol 20:20.
Laight DW, Desai KM, Gopaul NK, Anggard EE, Carrier MJ. (1999) F2-isoprostane evidence of oxidant stress in the insulin resistant, obese Zucker rat: effects of vitamin E. Eur J Pharmacol 377:8992.Lautt WW. (1999) The HISS story overview: a novel hepatic neurohumoral regulation of peripheral insulin sensitivity in health and diabetes. Can J Physiol Pharmacol 77:553-562.
Lautt WW. (2004) A new paradigm for diabetes and obesity: the hepatic insulin sensitizing substance
(HISS) hypothesis. J Pharmacol Sci 95:9-17.
Lavigne C, Marette A, Jacques H. (2000) Cod and soy proteins compared with casein improve glucose tolerance and insulin sensitivity in rats. Am J Physiol Endocrinol Metab 278:E491-500.
Lavigne C, Tremblay F, Asselin G, Jacques H, Marette A. (2001) Prevention of skeletal muscle insulin resistance by dietary cod protein in high fat-fed rats. Am J Physiol Endocrinol Metab 281:E6271.Lawrence JC, Jr. (1992) Signal transduction and protein phosphorylation in the regulation of cellular metabolism by insulin. Annu Rev Physiol 54:177-193.
Lawrence JC, Jr., Larner J. (1978) Activation of glycogen synthase in rat adipocytes by insulin and glucose involves increased glucose transport and phosphorylation. J Biol Chem 253:2104-2113.
Layman DK. (2003) The role of leucine in weight loss diets and glucose homeostasis. J Nutr
133 :261S-267S.
Layman DK. (2004) Protein quantity and quality at levels above the RDA improves adult weight loss.
J Am Coll Nutr 23:631S-636S.
Layman DK, Baum JI. (2004) Dietary protein impact on glycemic control during weight loss. J Nutr
134 :968S-973S.
Layman DK, Shiue H, Sather C, Erickson DJ, Baum J. (2003) Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss. J Nutr 133:405-410.
146Lee JI, Kang J, Stipanuk MH. (2006) Differential regulation of glutamate-cysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation. Biochem J
393 :181-190.
Lee JI, Londono M, Hirschberger LL, Stipanuk MH. (2004) Regulation of cysteine dioxygenase and gamma-glutamylcysteine synthetase is associated with hepatic cysteine level. J Nutr Biochem 15:112122.Lejeune MP, Westerterp KR, Adam TC, Luscombe-Marsh ND, Westerterp-Plantenga MS. (2006)
Ghrelin and glucagon-like peptide 1 concentrations, 24-h satiety, and energy and substrate metabolism during a high-protein diet and measured in a respiration chamber. Am J Clin Nutr 83:89-94.
Lentz SR, Sobey CG, Piegors DJ, Bhopatkar MY, Faraci FM, Malinow MR, Heistad DD. (1996)
Vascular dysfunction in monkeys with diet-induced hyperhomocyst(e)inemia. J Clin Invest 98:24-29.
Leung YM, Ahmed I, Sheu L, Gao X, Hara M, Tsushima RG, Diamant NE, Gaisano HY. (2006)
Insulin regulates islet alpha-cell function by reducing KATP channel sensitivity to adenosine 5'triphosphate inhibition. Endocrinology 147:2155-2162.
Levine RL, Williams JA, Stadtman ER, Shacter E. (1994) Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol 233:346-357.
L'Heureux-Bouron D, Tome D, Bensaid A, Morens C, Gaudichon C, Fromentin G. (2004a) A very high 70%-protein diet does not induce conditioned taste aversion in rats. J Nutr 134:1512-1515.
L'Heureux-Bouron D, Tome D, Bensaid A, Morens C, Lacroix M, Huneau JF, Fromentin G. (2004b)
Preabsorptive factors are not the main determinants of intake depression induced by a high-protein diet in the rat. Physiol Behav 81:499-504.
Li J, DeFea K, Roth RA. (1999) Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway. J Biol Chem 274:9351-9356.
Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, Tsuji H, Reaven GM, Cooke JP.
(2002) Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 106:987-992.
Lind C, Gerdes R, Schuppe-Koistinen I, Cotgreave IA. (1998) Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. Biochem Biophys Res Commun 247:481-486.
Ling PR, Mueller C, Smith RJ, Bistrian BR. (2003) Hyperglycemia induced by glucose infusion causes hepatic oxidative stress and systemic inflammation, but not STAT3 or MAP kinase activation in liver in rats. Metabolism 52:868-874.
Linn T, Geyer R, Prassek S, Laube H. (1996) Effect of dietary protein intake on insulin secretion and glucose metabolism in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 81:3938-3943.
Linn T, Santosa B, Gronemeyer D, Aygen S, Scholz N, Busch M, Bretzel RG. (2000) Effect of longterm dietary protein intake on glucose metabolism in humans. Diabetologia 43:1257-1265.
Liu YJ, Cheng H, Drought H, MacDonald MJ, Sharp GW, Straub SG. (2003) Activation of the KATP channel-independent signaling pathway by the nonhydrolyzable analog of leucine, BCH. Am J Physiol
Endocrinol Metab 285:E380-389.
147Liu Z, Wu Y, Nicklas EW, Jahn LA, Price WJ, Barrett EJ. (2004) Unlike insulin, amino acids stimulate p70S6K but not GSK-3 or glycogen synthase in human skeletal muscle. Am J Physiol
Endocrinol Metab 286:E523-528.
Lu SC, Ge JL, Kuhlenkamp J, Kaplowitz N. (1992) Insulin and glucocorticoid dependence of hepatic gamma-glutamylcysteine synthetase and glutathione synthesis in the rat. Studies in cultured hepatocytes and in vivo. J Clin Invest 90:524-532.
Lu SC, Kuhlenkamp J, Garcia-Ruiz C, Kaplowitz N. (1991) Hormone-mediated down-regulation of hepatic glutathione synthesis in the rat. J Clin Invest 88:260-269.
Lu SC, Sun WM, Yi J, Ookhtens M, Sze G, Kaplowitz N. (1996) Role of two recently cloned rat liver
GSH transporters in the ubiquitous transport of GSH in mammalian cells. J Clin Invest 97:1488-1496.
Lund S, Holman GD, Schmitz O, Pedersen O. (1995) Contraction stimulates translocation of glucose transporter GLUT4 in skeletal muscle through a mechanism distinct from that of insulin. Proc Natl
Acad Sci U S A 92:5817-5821.
Luscombe ND, Clifton PM, Noakes M, Parker B, Wittert G. (2002) Effects of energy-restricted diets containing increased protein on weight loss, resting energy expenditure, and the thermic effect of feeding in type 2 diabetes. Diabetes Care 25:652-657.
Lyons J, Rauh-Pfeiffer A, Yu YM, Lu XM, Zurakowski D, Tompkins RG, Ajami AM, Young VR,
Castillo L. (2000) Blood glutathione synthesis rates in healthy adults receiving a sulfur amino acidfree diet. Proc Natl Acad Sci U S A 97:5071-5076.
Ma SW, Tomlinson B, Benzie IF. (2005) A study of the effect of oral glucose loading on plasma oxidant:antioxidant balance in normal subjects. Eur J Nutr 44:250-254.
Maechler P, Kennedy ED, Pozzan T, Wollheim CB. (1997) Mitochondrial activation directly triggers the exocytosis of insulin in permeabilized pancreatic beta-cells. Embo J 16:3833-3841.
Malaisse WJ, Hutton JC, Carpinelli AR, Herchuelz A, Sener A. (1980) The stimulus-secretion coupling of amino acid-induced insulin release: metabolism and cationic effects of leucine. Diabetes
29 :431-437.
Malmezat T, Breuille D, Capitan P, Mirand PP, Obled C. (2000) Glutathione turnover is increased during the acute phase of sepsis in rats. J Nutr 130:1239-1246.
Manders RJ, Wagenmakers AJ, Koopman R, Zorenc AH, Menheere PP, Schaper NC, Saris WH, van
Loon LJ. (2005) Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes. Am J Clin Nutr 82:76-83.
Manning PJ, Sutherland WH, Walker RJ, Williams SM, De Jong SA, Ryalls AR, Berry EA. (2004)
Effect of high-dose vitamin E on insulin resistance and associated parameters in overweight subjects.
Diabetes Care 27:2166-2171.
Manzella D, Grella R, Esposito K, Cacciapuoti F, Arciello A, Giugliano D, Paolisso G. (2005) Oral amino acid administration decreases oxidative stress and improves brachial reactivity in elderly individuals. Am J Hypertens 18:858-863.
Marfella R, Quagliaro L, Nappo F, Ceriello A, Giugliano D. (2001) Acute hyperglycemia induces an oxidative stress in healthy subjects. J Clin Invest 108:635-636.
148Mariotti F, Simbelie KL, Makarios-Lahham L, Huneau JF, Laplaize B, Tome D, Even PC. (2004)
Acute ingestion of dietary proteins improves post-exercise liver glutathione in rats in a dosedependent relationship with their cysteine content. J Nutr 134:128-131.
Martin F, Soria B. (1995) Amino acid-induced [Ca2+]i oscillations in single mouse pancreatic islets of Langerhans. J Physiol 486:361-371.
Matsuda M, DeFronzo RA. (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462-1470.
May JM, de Haen C. (1979a) The insulin-like effect of hydrogen peroxide on pathways of lipid synthesis in rat adipocytes. J Biol Chem 254:9017-9021.
May JM, de Haen C. (1979b) Insulin-stimulated intracellular hydrogen peroxide production in rat epididymal fat cells. J Biol Chem 254:2214-2220.
McArthur LH, Kelly WF, Gietzen DW, Rogers QR. (1993) The role of palatability in the food intake response of rats fed high-protein diets. Appetite 20:181-196.
McKeown NM, Meigs JB, Liu S, Saltzman E, Wilson PW, Jacques PF. (2004) Carbohydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring
Cohort. Diabetes Care 27:538-546.
McSorley PT, Bell PM, Young IS, Atkinson AB, Sheridan B, Fee JP, McCance DR. (2005)
Endothelial function, insulin action and cardiovascular risk factors in young healthy adult offspring of parents with Type 2 diabetes: effect of vitamin E in a randomized double-blind, controlled clinical trial. Diabet Med 22:703-710.
Meakins TS, Persaud C, Jackson AA. (1998) Dietary supplementation with L-methionine impairs the utilization of urea-nitrogen and increases 5-L-oxoprolinuria in normal women consuming a low protein diet. J Nutr 128:720-727.
Melancon S, Bachelard H, Badeau M, Bourgoin F, Pitre M, Lariviere R, Nadeau A. (2006) Effects of high-sucrose feeding on insulin resistance and hemodynamic responses to insulin in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 290:H2571-2581.
Menon V, Ram M, Dorn J, Armstrong D, Muti P, Freudenheim JL, Browne R, Schunemann H,
Trevisan M. (2004) Oxidative stress and glucose levels in a population-based sample. Diabet Med
21 :1346-1352.
Metges CC, Yu YM, Cai W, Lu XM, Wong S, Regan MM, Ajami A, Young VR. (2000) Oxoproline kinetics and oxoproline urinary excretion during glycine- or sulfur amino acid-free diets in humans.
Am J Physiol Endocrinol Metab 278:E868-876.
Meyer C, Dostou JM, Gerich JE. (1999) Role of the human kidney in glucose counterregulation.
Diabetes 48:943-948.
Meyer KA, Kushi LH, Jacobs DR, Jr., Slavin J, Sellers TA, Folsom AR. (2000) Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr 71:921-930.
Micke P, Beeh KM, Buhl R. (2002) Effects of long-term supplementation with whey proteins on plasma glutathione levels of HIV-infected patients. Eur J Nutr 41:12-18.
149Midaoui AE, Elimadi A, Wu L, Haddad PS, de Champlain J. (2003) Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am J
Hypertens 16:173-179.
Minehira K, Vega N, Vidal H, Acheson K, Tappy L. (2004) Effect of carbohydrate overfeeding on whole body macronutrient metabolism and expression of lipogenic enzymes in adipose tissue of lean and overweight humans. Int J Obes Relat Metab Disord 28:1291-1298.
Moellering D, McAndrew J, Patel RP, Cornwell T, Lincoln T, Cao X, Messina JL, Forman HJ, Jo H,
Darley-Usmar VM. (1998) Nitric oxide-dependent induction of glutathione synthesis through increased expression of gamma-glutamylcysteine synthetase. Arch Biochem Biophys 358:74-82.
Moldeus P, Cotgreave IA. (1994) N-acetylcysteine. Methods Enzymol 234:482-492.
Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. Jama 295:1681-1687.
Moran LJ, Luscombe-Marsh ND, Noakes M, Wittert GA, Keogh JB, Clifton PM. (2005) The satiating effect of dietary protein is unrelated to postprandial ghrelin secretion. J Clin Endocrinol Metab
90 :5205-5211.
Morand C, Rios L, Moundras C, Besson C, Remesy C, Demigne C. (1997) Influence of methionine availability on glutathione synthesis and delivery by the liver. J Nutr Biochem 8:246-255.
Morens C, Gaudichon C, Fromentin G, Marsset-Baglieri A, Bensaid A, Larue-Achagiotis C, Luengo
C, Tome D. (2001) Daily delivery of dietary nitrogen to the periphery is stable in rats adapted to increased protein intake. Am J Physiol Endocrinol Metab 281:E826-836.
Moriarty-Craige SE, Jones DP. (2004) Extracellular thiols and thiol/disulfide redox in metabolism.
Annu Rev Nutr 24:481-509.
Morifuji M, Sakai K, Sanbongi C, Sugiura K. (2005) Dietary whey protein increases liver and skeletal muscle glycogen levels in exercise-trained rats. Br J Nutr 93:439-445.
Moundras C, Remesy C, Demigne C. (1993) Dietary protein paradox: decrease of amino acid availability induced by high-protein diets. Am J Physiol 264:G1057-1065.
Mudd SH, Finkelstein JD, Irreverre F, Laster L. (1965) Transsulfuration in mammals. Microassays and tissue distributions of three enzymes of the pathway. J Biol Chem 240:4382-4392.
Mukherjee SP, Lynn WS. (1977) Reduced nicotinamide adenine dinucleotide phosphate oxidase in adipocyte plasma membrane and its activation by insulin. Possible role in the hormone's effects on adenylate cyclase and the hexose monophosphate shunt. Arch Biochem Biophys 184:69-76.
Nagai Y, Nishio Y, Nakamura T, Maegawa H, Kikkawa R, Kashiwagi A. (2002) Amelioration of high fructose-induced metabolic derangements by activation of PPARalpha. Am J Physiol Endocrinol
Metab 282:E1180-1190.
Nandhini AT, Thirunavukkarasu V, Ravichandran MK, Anuradha CV. (2005) Effect of taurine on biomarkers of oxidative stress in tissues of fructose-fed insulin-resistant rats. Singapore Med J 46:8287.Naruse K, Rask-Madsen C, Takahara N, Ha SW, Suzuma K, Way KJ, Jacobs JR, Clermont AC, Ueki
K, Ohshiro Y, Zhang J, Goldfine AB, King GL. (2006) Activation of vascular protein kinase C-beta
150inhibits Akt-dependent endothelial nitric oxide synthase function in obesity-associated insulin resistance. Diabetes 55:691-698.
Newgard CB, Moore SV, Foster DW, McGarry JD. (1984) Efficient hepatic glycogen synthesis in refeeding rats requires continued carbon flow through the gluconeogenic pathway. J Biol Chem
259 :6958-6963.
Newsholme P, Brennan L, Rubi B, Maechler P. (2005) New insights into amino acid metabolism, beta-cell function and diabetes. Clin Sci (Lond) 108:185-194.
Nicolaidis S, Rowland N, Meile MJ, Marfaing-Jallat P, Pesez A. (1974) A flexible technique for long term infusions in unrestrained rats. Pharmacol Biochem Behav 2:131-136.
Nijpels G, van der Wal PS, Bouter LM, Heine RJ. (1994) Comparison of three methods for the quantification of beta-cell function and insulin sensitivity. Diabetes Res Clin Pract 26:189-195.
Nilsson M, Stenberg M, Frid AH, Holst JJ, Bjorck IM. (2004) Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins. Am J Clin Nutr 80:1246-1253.
Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D,
Oates PJ, Hammes HP, Giardino I, Brownlee M. (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787-790.
Nishitani S, Matsumura T, Fujitani S, Sonaka I, Miura Y, Yagasaki K. (2002) Leucine promotes glucose uptake in skeletal muscles of rats. Biochem Biophys Res Commun 299:693-696.
Nishitani S, Takehana K, Fujitani S, Sonaka I. (2005) Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol 288:G1292-1300.
Nkabyo YS, Gu LH, Jones DP, Ziegler TR. (2006) Thiol/disulfide redox status is oxidized in plasma and small intestinal and colonic mucosa of rats with inadequate sulfur amino acid intake. J Nutr
136 :1242-1248.
Nomiyama T, Igarashi Y, Taka H, Mineki R, Uchida T, Ogihara T, Choi JB, Uchino H, Tanaka Y,
Maegawa H, Kashiwagi A, Murayama K, Kawamori R, Watada H, Bannai S, Kitamura E. (2004)
Reduction of insulin-stimulated glucose uptake by peroxynitrite is concurrent with tyrosine nitration of insulin receptor substrate-1
Transport interaction of L-cystine and L-glutamate in human diploid fibroblasts in culture. Biochem
Biophys Res Commun 320:639-647.
Nuttall FQ, Gannon MC. (1991) Plasma glucose and insulin response to macronutrients in nondiabetic and NIDDM subjects. Diabetes Care 14:824-838.
Nuttall FQ, Gannon MC, Jordan K. (2004) The metabolic response to ingestion of proline with and without glucose. Metabolism 53:241-246.
Nuttall FQ, Mooradian AD, Gannon MC, Billington C, Krezowski P. (1984) Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load. Diabetes Care
7 :465-470.
Ogihara T, Asano T, Katagiri H, Sakoda H, Anai M, Shojima N, Ono H, Fujishiro M, Kushiyama A,
Fukushima Y, Kikuchi M, Noguchi N, Aburatani H, Gotoh Y, Komuro I, Fujita T. (2004) Oxidative stress induces insulin resistance by activating the nuclear factor-kappa B pathway and disrupting normal subcellular distribution of phosphatidylinositol 3-kinase. Diabetologia 47:794-805.
151Ohneda A, Parada E, Eisentraut AM, Unger RH. (1968) Characterization of response of circulating glucagon to intraduodenal and intravenous administration of amino acids. J Clin Invest 47:2305-2322.
Olson LK, Redmon JB, Towle HC, Robertson RP. (1993) Chronic exposure of HIT cells to high glucose concentrations paradoxically decreases insulin gene transcription and alters binding of insulin gene regulatory protein. J Clin Invest 92:514-519.
Ookhtens M, Kaplowitz N. (1998) Role of the liver in interorgan homeostasis of glutathione and cyst(e)ine. Semin Liver Dis 18:313-329.
Pacy PJ, Price GM, Halliday D, Quevedo MR, Millward DJ. (1994) Nitrogen homeostasis in man: the diurnal responses of protein synthesis and degradation and amino acid oxidation to diets with increasing protein intakes. Clin Sci (Lond) 86:103-116.
Pagliassotti MJ, Prach PA. (1997) Increased net hepatic glucose output from gluconeogenic precursors after high-sucrose diet feeding in male rats. Am J Physiol 272:R526-531.
Pagliassotti MJ, Prach PA, Koppenhafer TA, Pan DA. (1996) Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats. Am J Physiol 271:R1319-1326.
Paolisso G, D'Amore A, Giugliano D, Ceriello A, Varricchio M, D'Onofrio F. (1993) Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. Am J Clin Nutr 57:650-656.
Paolisso G, Di Maro G, Pizza G, D'Amore A, Sgambato S, Tesauro P, Varricchio M, D'Onofrio F.
(1992a) Plasma GSH/GSSG affects glucose homeostasis in healthy subjects and non-insulindependent diabetics. Am J Physiol 263:E435-440.
Paolisso G, Giugliano D, Pizza G, Gambardella A, Tesauro P, Varricchio M, D'Onofrio F. (1992b)
Glutathione infusion potentiates glucose-induced insulin secretion in aged patients with impaired glucose tolerance. Diabetes Care 15:1-7.
Papakonstantinou E, Panagiotakos DB, Pitsavos C, Chrysohoou C, Zampelas A, Skoumas Y,
Stefanadis C. (2005) Food group consumption and glycemic control in people with and without type 2
diabetes: the ATTICA study. Diabetes Care 28:2539-2540.
Parker B, Noakes M, Luscombe N, Clifton P. (2002) Effect of a high-protein, high-monounsaturated fat weight loss diet on glycemic control and lipid levels in type 2 diabetes. Diabetes Care 25:425-430.
Parks EJ. (2002) Dietary carbohydrate's effects on lipogenesis and the relationship of lipogenesis to blood insulin and glucose concentrations. Br J Nutr 87 Suppl 2:S247-253.
Pastore A, Federici G, Bertini E, Piemonte F. (2003) Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta 333:19-39.
Patti ME, Brambilla E, Luzi L, Landaker EJ, Kahn CR. (1998) Bidirectional modulation of insulin action by amino acids. J Clin Invest 101:1519-1529.
Pawlak DB, Kushner JA, Ludwig DS. (2004) Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animals. Lancet 364:778-785.
Peret J, Chanez M, Cota J, Macaire I. (1975) Effects of quantity and quality of dietary protein and variation in certain enzyme activities on glucose metabolism in the rat. J Nutr 105:1525-1534.
152Pessin JE, Saltiel AR. (2000) Signaling pathways in insulin action: molecular targets of insulin resistance. J Clin Invest 106:165-169.
Peters LP, Teel RW. (2003) Effects of high sucrose diet on body and liver weight and hepatic enzyme content and activity in the rat. In Vivo 17:61-65.
Petrie JR, Ueda S, Webb DJ, Elliott HL, Connell JM. (1996

Table of content

TABLE DES MATIERES
LISTE DES FIGURES - 7
LISTE DES TABLEAUX - 10
LISTE DES ABREVIATIONS - 11
LISTE DES PUBLICATIONS - 13
INTRODUCTION BIBLIOGRAPHIQUE - 14
INTRODUCTION GENERALE - 15
A. APPORT EN ACIDES AMINES SOUFRES ET MODULATION DU STATUT EN
GLUTATHION - 18
1. LE GLUTATHION ET LE STATUT REDOX - 18
1.1. Le glutathion dans l'organisme - 18
1.1.1. La synthèse de glutathion - 18
1.1.2. La régulation de la synthèse de glutathion - 19
1.1.3. Les pools de glutathion et son turnover - 21
1.2. Les rôles du glutathion dans la cellule - 23
1.2.1. Le glutathion et le statut redox intracellulaire - 24
1.2.2. Participation aux défenses antioxydantes et à la détoxification - 26
1.2.3. La glutathionylation et l'équilibre thiol/disulfure - 26
2. APPORT EN ACIDES AMINES SOUFRES ET STATUT EN GLUTATHION - 29
2.1. Rappels sur le métabolisme des acides aminés soufrés - 29
2.1.1. Les voies de transméthylation et transsulfuration - 29
2.1.2. Les voies d'utilisation de la cystéine - 30
2.2. Apport protéique et modulation de la synthèse et du turnover du glutathion : conséquences sur le statut en glutathion - 32
2.2.1. Apport protéique et modulation de la synthèse de glutathion - 32
2.2.2. Les mécanismes de l'effet des acides aminés sur la synthèse de glutathion - 35
B. INFLUENCE DU STATUT EN GLUTATHION SUR LA REGULATION
GLYCEMIQUE - 36
1. RAPPELS SUR LA VOIE DE SIGNALISATION DE L'INSULINE ET LES MECANISMES DE LA
CAPTATION PERIPHERIQUE DE GLUCOSE - 36
52. STATUT REDOX, REGULATION GLYCEMIQUE ET INSULINO-RESISTANCE - 38
2.1. La voie de signalisation de l'insuline et le statut redox intracellulaire - 38
2.2. Rôle du stress oxydant dans la physiopathologie de l'insulino-résistance - 40
2.3. Le stress oxydant au cours de la période postprandiale - 41
2.4. Stress oxydant, hyperglycémie et altération de la fonction sécrétoire des cellules β pancréatiques et de la fonction endothéliale - 43
3. LE STATUT EN GLUTATHION ET LA REGULATION GLYCEMIQUE - 44
4. APPORT EN ACIDES AMINES SOUFRES ET REGULATION GLYCEMIQUE - 46
C. AUTRES MECANISMES D'ACTION DES ACIDES AMINES ET DES PROTEINES
ALIMENTAIRES SUR LA REGULATION GLYCEMIQUE - 50
1. ACIDES AMINES, PROTEINES ALIMENTAIRES ET PRODUCTION ENDOGENE DE GLUCOSE - 50
1.1. Rappels sur la production endogène de glucose et sa régulation - 50
1.2. Rôle des acides aminés comme précurseur dans la néoglucogenèse - 51
1.3. Effet aigu de l'ingestion d'un repas protéique sur la production endogène de glucose - 52
1.4. Effet de l'adaptation à une alimentation hyperprotéique sur la production endogène de glucose - 53
2. ACIDES AMINES, PROTEINES ALIMENTAIRES ET FONCTION ENDOCRINE PANCREATIQUE - 55
2.1. Mise en évidence d'un effet insulino-sécréteur des acides aminés - 55
2.2. Rappels sur les mécanismes de sécrétion d'insuline - 56
2.3. Modes d'actions des acides aminés sur la sécrétion d'insuline - 56
2.3.1. Le transport électrogénique des acides aminés - 57
2.3.2. Le métabolisme intracellulaire des acides aminés - 58
2.3.3. Effets indirects des protéines alimentaires sur la sécrétion d'insuline et de glucagon par l'intermédiaire des hormones incrétines - 59
2.4. Effet des protéines alimentaires sur la sécrétion d'insuline - 60
2.4.1. Effets aigus de l'ingestion d'un repas protéique sur la sécrétion d'insuline - 60
2.4.2. Effets d'une alimentation hyperprotéique sur la sécrétion d'insuline - 60
3. ACIDES AMINES, PROTEINES ALIMENTAIRES, CAPTATION PERIPHERIQUE DE GLUCOSE ET
SENSIBILITE A L'INSULINE - 62
63.1. Mise en évidence d'un effet des acides aminés sur la sensibilité à l'insuline in vivo
623.2. Mécanismes de la modulation du transport de glucose par les acides aminés - 63
3.2.1. Acides aminés et voie de signalisation de l'insuline - 63
3.2.2. Acides aminés et utilisation métabolique du glucose - 65
3.2.3. Acides aminés et microcirculation périphérique - 67
3.3. Régimes hyperprotéiques et sensibilité à l'insuline - 68
3.3.1. Effet d'une alimentation HP normo-énergétique sur la sensibilité à l'insuline - 68
3.3.2. Effet d'une alimentation HP hypoénergétique sur la sensibilité à l'insuline - 70
3.3.3. Effet de la qualité des protéines alimentaires sur l'insulino-sensibilité - 71
CONCLUSIONS ET JUSTIFICATION DES TRAVAUX EXPERIMENTAUX - 74
TRAVAUX PERSONNELS - 78
ARTICLE 1 - 79
RESULTATS COMPLEMENTAIRES DES EXPERIENCES DE L'ARTICLE 1 - 83
ARTICLE 2 - 88
ARTICLE 3 - 91
RESULTATS COMPLEMENTAIRES DES EXPERIENCES DE L'ARTICLE 3 - 94
ARTICLE 4 - 98
DISCUSSION GENERALE - 101
ANNEXES - 123
ARTICLE 5 - 124
ARTICLE 6 - 127
RÉFÉRENCES BIBLIOGRAPHIQUES - 130

Statistiques de consultation

Repository Staff Only: edit this item