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Hyperaminoacidaemia at postprandial levels does not modulate glucose metabolism in type 2 diabetes mellitus.
MedLine Citation:
PMID:  21437771     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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-(3)H]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.
Authors:
M Bassil; S Burgos; E B Marliss; J A Morais; S Chevalier; R Gougeon
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-25
Journal Detail:
Title:  Diabetologia     Volume:  -     ISSN:  1432-0428     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
McGill Nutrition and Food Science Centre, MUHC/Royal Victoria Hospital, 687 Pine Avenue West, H6.61, Montreal, QC, Canada H3A 1A1.
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