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-[1-13C]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). Results: In Hyper-2 vs Hyper-1 clamps, leucine flux (2.99± 0.16 vs 2.62±0.06 μmolkg [fat-free mass (FFM)]-1min-1), rates of synthesis (2.31±0.15 vs 1.98±0.06) and breakdown (2.38±0.16 vs 2.00±0.07) were higher (p<0.05), but leucine oxidation and net balance did not differ. In Hyper-3 vs Hyper-2 clamps, leucine flux and synthesis and oxidation rates increased markedly as did net balance (0.84±0.09 vs -0.07±0.04 μmol [kg FFM]-1min -1, p<0.0001). Conclusions/interpretation: In type 2 diabetic men, insulin resistance of protein metabolism is of the same magnitude 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. © Springer-Verlag 2010.