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Diabetologia

Erschienen in:

01.07.2011 | Article

Hyperaminoacidaemia at postprandial levels does not modulate glucose metabolism in type 2 diabetes mellitus

verfasst von: M. Bassil, S. Burgos, E. B. Marliss, J. A. Morais, S. Chevalier, R. Gougeon

Erschienen in: Diabetologia | Ausgabe 7/2011

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Abstract

Aims/hypothesis

Hyperaminoacidaemia attenuates glucose disposal during hyperinsulinaemic clamps in healthy lean individuals, an effect thought to be mediated by negative feedback on insulin signalling, downstream of the mammalian target of rapamycin (mTOR) signalling pathway. This has been interpreted as amino acids causing insulin resistance in healthy people, and contributing to it in type 2 diabetes. However, the effect of hyperaminoacidaemia on glucose disposal in type 2 diabetic individuals remains to be determined.

Methods

Eight obese men with type 2 diabetes underwent a two-step hyperinsulinaemic–hyperglycaemic (8 mmol/l) clamp, first with amino acids at postabsorptive concentrations, followed by postprandial concentrations. Whole-body glucose turnover was assessed using d-[3-³H]glucose. Vastus lateralis biopsies were obtained at baseline and during each step of the clamp to determine the phosphorylation states of AKT, mTOR, ribosomal protein (rp) S6, and insulin receptor substrate (IRS)-1.

Results

Rates of glucose infusion (1.30 ± 0.19 vs 1.15 ± 0.13 mmol/min), endogenous glucose production (0.48 ± 0.06 vs 0.53 ± 0.05 mmol/min) and disposal (1.24 ± 0.17 vs 1.17 ± 0.14 mmol/min) did not differ between postabsorptive and postprandial amino acid concentrations (p > 0.05). Whereas phosphorylation of AKT^Ser473, AKT^Thr308 mTOR^Ser2448 and rpS6^Ser235/236 increased (p < 0.05) with elevated amino acids, that of IRS-1^Ser636/639 and IRS-1^Ser1101 did not change.

Conclusions/interpretation

Postprandial circulating amino acid concentrations do not worsen the already attenuated glucose disposal in hyperglycaemic type 2 diabetic men, and cell-signalling events are consistent with this. Our results do not support recommendations to restrict dietary protein in type 2 diabetes.

Skilton MR, Laville M, Cust AE, Moulin P, Bonnet F (2008) The association between dietary macronutrient intake and the prevalence of the metabolic syndrome. Br J Nutr 100:400–407PubMedCrossRef

Schulze MB, Manson JE, Willett WC, Hu FB (2003) Processed meat intake and incidence of type 2 diabetes in younger and middle-aged women. Diabetologia 46:1465–1473PubMedCrossRef

Liese AD, Weis KE, Schulz M, Tooze JA (2009) Food intake patterns associated with incident type 2 diabetes: the Insulin Resistance Atherosclerosis Study. Diab Care 32:263–268CrossRef

Promintzer M, Krebs M (2006) Effects of dietary protein on glucose homeostasis. Curr Opin Clin Nutr Metab Care 9:463–468PubMedCrossRef

Traxinger RR, Marshall S (1989) Role of amino acids in modulating glucose-induced desensitization of the glucose transport system. J Biol Chem 264:20910–20916PubMed

Tremblay F, Marette A (2001) Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. J Biol Chem 276:38052–38060PubMed

Tremblay F, Gagnon A, Veilleux A, Sorisky A, Marette A (2005) Activation of the mammalian target of rapamycin pathway acutely inhibits insulin signaling to Akt and glucose transport in 3T3-L1 and human adipocytes. Endocrinology 146:1328–1337PubMedCrossRef

Pisters PW, Restifo NP, Cersosimo E, Brennan MF (1991) The effects of euglycemic hyperinsulinemia and amino acid infusion on regional and whole body glucose disposal in man. Metabolism 40:59–65PubMedCrossRef

Tremblay F, Krebs M, Dombrowski L et al (2005) Overactivation of S6 kinase 1 as a cause of human insulin resistance during increased amino acid availability. Diabetes 54:2674–2684PubMedCrossRef

10.

Krebs M, Brunmair B, Brehm A et al (2007) The mammalian target of rapamycin pathway regulates nutrient-sensitive glucose uptake in man. Diabetes 56:1600–1607PubMedCrossRef

11.

Adegoke OAJ, Chevalier S, Morais JA et al (2009) Fed-state clamp stimulates cellular mechanisms of muscle protein anabolism and modulates glucose disposal in normal men. Am J Physiol Endocrinol Metab 296:E105–113PubMedCrossRef

12.

Krebs M, Krssak M, Bernroider E et al (2002) Mechanism of amino acid-induced skeletal muscle insulin resistance in humans. Diabetes 51:599–605PubMedCrossRef

13.

Schwenk WF, Haymond MW (1987) Decreased uptake of glucose by human forearm during infusion of leucine, isoleucine, or threonine. Diabetes 36:199–204PubMedCrossRef

14.

Flakoll PJ, Wentzel LS, Rice DE, Hill JO, Abumrad NN (1992) Short-term regulation of insulin-mediated glucose utilization in four-day fasted human volunteers: role of amino acid availability. Diabetologia 35:357–366PubMedCrossRef

15.

Felig P, Marliss E, Ohman JL, Cahill GF Jr (1970) Plasma amino acid levels in diabetic ketoacidosis. Diabetes 19:727–728PubMed

16.

Pereira S, Marliss EB, Morais JA, Chevalier S, Gougeon R (2008) Insulin resistance of protein metabolism in type 2 diabetes. Diabetes 57:56–63PubMedCrossRef

17.

Gannon MC, Nuttall FQ (2004) Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. Diabetes 53:2375–2382PubMedCrossRef

18.

Gannon MC, Nuttall FQ (2006) Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition. Nutr Metab (Lond) 3:16CrossRef

19.

Nuttall FQ, Gannon MC (2006) The metabolic response to a high-protein, low-carbohydrate diet in men with type 2 diabetes mellitus. Metabolism 55:243–251PubMedCrossRef

20.

Nuttall FQ, Schweim K, Hoover H, Gannon MC (2008) Effect of the LoBAG30 diet on blood glucose control in people with type 2 diabetes. Br J Nutr 99:511–519PubMedCrossRef

21.

Manders RJF, Wagenmakers AJM, Koopman R et al (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 82:76–83PubMed

22.

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 78:734–741PubMed

23.

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. Diab Care 7:465–470CrossRef

24.

Tremblay F, Brûlé S, Hee Um S et al (2007) Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance. Proc Natl Acad Sci 104:14056–14061PubMedCrossRef

25.

Patti ME, Brambilla E, Luzi L, Landaker EJ, Kahn CR (1998) Bidirectional modulation of insulin action by amino acids. J Clin Investig 101:1519–1529PubMedCrossRef

26.

World Health Organization (1995) Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. The Organization, Geneva

27.

Chevalier S, Gougeon R, Kreisman SH, Cassis C, Morais JA (2004) The hyperinsulinemic amino acid clamp increases whole-body protein synthesis in young subjects. Metabolism 53:388–396PubMedCrossRef

28.

Sigal RJ, Purdon C, Fisher SJ, Halter JB, Vranic M, Marliss EB (1994) Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects. J Clin Endocrinol Metab 79:1049–1057PubMedCrossRef

29.

Bradley DC, Steil GM, Bergman RN (1993) Quantitation of measurement error with optimal segments: basis for adaptive time course smoothing. Am J Physiol 264:E902–911PubMed

30.

Chevalier S, Marliss EB, Morais JA, Lamarche M, Gougeon R (2005) Whole-body protein anabolic response is resistant to the action of insulin in obese women. Am J Clin Nutr 82:355–365PubMed

31.

Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedCrossRef

32.

Lachin JM (1981) Introduction to sample size determination and power analysis for clinical trials. Control Clin Trials 2:93–113PubMedCrossRef

33.

Esteghamati A, Ashraf H, Khalilzadeh O et al (2010) Optimal cut-off of homeostasis model assessment of insulin resistance (HOMA-IR) for the diagnosis of metabolic syndrome: third national surveillance of risk factors of non-communicable diseases in Iran (SuRFNCD-2007). Nutr Metab (Lond) 7:26CrossRef

34.

Mourad C, Chevalier S, Morais JA, Lamarche M, Gougeon R (2009) Antihyperglycaemic medication modifies factors of postprandial satiety in type 2 diabetes. Diabetes Obes Metab 11:819–822PubMedCrossRef

35.

Muoio DM, Newgard CB (2008) Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 9:193–205PubMedCrossRef

36.

Gual P, Le Marchand-Brustel Y, Tanti J-F (2005) Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochimie 87:99–109PubMedCrossRef

37.

Frojdo S, Vidal H, Pirola L (2009) Alterations of insulin signaling in type 2 diabetes: a review of the current evidence from humans. Biochim Biophys Acta 1792:83–92PubMed

38.

Bouzakri K, Roques M, Gual P et al (2003) Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes. Diabetes 52:1319–1325PubMedCrossRef

39.

Hay N (2005) The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8:179–183PubMedCrossRef

40.

Chevalier S, Marliss EB, Morais JA, Lamarche M, Gougeon R (2005) The influence of sex on the protein anabolic response to insulin. Metabolism 54:1529–1535PubMedCrossRef

41.

Bassil M, Marliss EB, Morais JA, Pereira S, Chevalier S, Gougeon R (2011) Postprandial hyperaminoacidaemia overcomes insulin resistance of protein anabolism in men with type 2 diabetes. Diabetologia 54:648–656PubMedCrossRef

Titel: Hyperaminoacidaemia at postprandial levels does not modulate glucose metabolism in type 2 diabetes mellitus
verfasst von: M. Bassil
S. Burgos
E. B. Marliss
J. A. Morais
S. Chevalier
R. Gougeon
Publikationsdatum: 01.07.2011
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 7/2011
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2115-7

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