Journal
DIABETOLOGIA
Volume 54, Issue 7, Pages 1810-1818Publisher
SPRINGER
DOI: 10.1007/s00125-011-2115-7
Keywords
Glucose disposal; Glucose metabolism; Glucose turnover; Hyperaminoacidaemia; Hyperinsulinaemic clamp; Insulin resistance; Type 2 diabetes
Categories
Funding
- Canadian Institutes of Health Research [MOP-77562]
- McGill University Health Centre Research Institute
- Fonds de recherche en sante du Quebec
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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. 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-H-3]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. 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. 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.
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