Postprandial hyperaminoacidaemia overcomes insulin resistance of protein anabolism in men with type 2 diabetes

Abstract

Aims/hypothesis Although protein is usually ignored when considering insulin resistance, we have shown resistance of protein concurrent with glucose metabolism in men with type 2 diabetes during a hyperinsulinaemic clamp at euglycaemia and fasting aminoacidaemia. We hypothesised that this resistance is even worse during conditions that simulate the postprandial state, when anabolism should be maximal. Methods Eight overweight and obese men with type 2 diabetes underwent a hyperinsulinaemic-hyperglycaemic (8 mmol/l) clamp, first with plasma amino acids at postabsorptive (Hyper-2) then at postprandial concentrations (Hyper-3). Whole-body protein kinetics were assessed using L-[1-13 C]leucine. Hyper-2 results were compared with those of diabetic men whose plasma glucose was lowered to 5.5 mmol/l and fasting aminoacidaemia maintained during the hyperinsulinaemic clamp (Hyper-1 at 8 vs 5.5 mmol/l, but turnover rates are higher with hyperglycaemia. Contrary to our hypothesis, sustained postprandial-level hyperaminoacidaemia stimulated positive net protein balance comparable with that previously found in lean non-diabetic men. This was sufficient to overcome the insulin resistance of protein anabolism.

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

“…These findings, together with the evidence of impaired protein metabolism in diabetes [16] that is overcome by generous protein provision [41], do not support recommendations to restrict protein intake.…”

Effect of obesity and type 2 diabetes on protein anabolic response to insulin in elderly women

“…We showed that amino acids can overcome the insulin resistance of protein metabolism through their anabolic action (Bassil et al, 2011a) without further impairing glucose metabolism in obese middle-aged men with type 2 diabetes (Bassil et al, 2011b). Moreover, a recent systematic review and meta-analysis of 20 randomized controlled trials investigating dietary approaches in the management of type 2 diabetes indicated that high-protein diets are among the few approaches that are effective in improving glycemic control (Ajala et al, 2013).…”

Protein and glucose metabolic responses to hyperinsulinemia, hyperglycemia, and hyperaminoacidemia in obese men

“…The [ 2 H 5 ]phenylalanine infusion started 1.5 h before the other isotopes, then all continued for 6 h, with clamp from 4.5 to 7.5 h with: human insulin (primed, then 0.98‐1.3 mU [kg FFM −1 ] min −1 , Humulin R; Eli Lilly Canada Inc, Toronto, ON, Canada); octreotide (35.3 ng [kg FFM −1 ] min −1 , Omega, Montreal, QC, Canada); glucagon (0.94 ng [kg FFM −1 ] min −1 , Eli Lilly); and human growth hormone (hGH; 3.53 ng [kg FFM −1 ] min −1 , Saizen, EMD Serono, Canada). Concurrently, 20% low‐enriched 1 3 C‐glucose (Avebe b.a., Foxhol, Netherlands) and 10% AA solution (TrophAmine, B. Braun Medical, Irvine, CA) were infused at variable rates to clamp glucose at 8 mmol l −1 and branched‐chain amino acids (BCAA), at postprandial concentrations , both based on 5‐min interval measurements. Blood was collected hourly for substrates, hormones, and isotopic enrichment and at 10‐min intervals from 2.5‐3 h to 5.5–6 h. L‐[1‐ 13 C] leucine kinetics were calculated using plasma 1‐[ 13 C] α‐ketoisocaproic acid (KIC) enrichment (reciprocal model) .…”