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


RESULTS
In Hyper-2 vs Hyper-1 clamps, leucine flux (2.99 ± 0.16 vs 2.62 ± 0.06 μmol kg [fat-free mass (FFM)](-1) min(-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](-1) min(-1), p < 0.0001).


CONCLUSIONS
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.
McGill University Nutrition and Food Science Centre, McGill University Health Centre/Royal Victoria Hospital, 687 Pine Avenue West, H6.61, Montreal, QC, Canada.
M
M
Bassil
E B
EB
Marliss
J A
JA
Morais
S
S
Pereira
S
S
Chevalier
R
R
Gougeon
D000596:Amino Acids / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011506:Proteins / Q000378:metabolism*
D000596:Amino Acids; D011506:Proteins