Lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic subjects

Skeletal muscle uncoupling protein 2 and 3 (UCP-2 and UCP-3) mRNA levels ar e increased during calorie restriction in lean and nondiabetic obese subjec ts. In this work, we have investigated the effect of a 5-day hypocaloric di et (1,045 kJ/day) on UCP-2 and UCP-3 gene expression in the skeletal muscle of type-2 diabetic obese patients. Before the diet, UCP-2 and UCP-3 mRNA l evels were more abundant in diabetic than in nondiabetic subjects. The long (UCP-3(L)) and short (UCP-3(S)) forms of UCP-3 transcripts were expressed at similar levels in nondiabetic subjects, but UCP-3(S) transcripts were tw ofold more abundant than UCP-3L transcripts in the muscle of diabetic patie nts. Calorie restriction induced a two- to threefold increase in UCP-2 and UCP-3 mRNA levels in nondiabetic patients. No change was observed in type-2 diabetic patients. Variations in plasma nonesterified fatty acid level wer e positively correlated with changes in skeletal muscle UCP-3(L) (r = 0.6, P < 0.05) and adipose tissue hormone-sensitive lipase (r = 0.9, P < 0.001) mRNA levels. Lack of increase in plasma nonesterified fatty acid level and in hormone-sensitive lipase upregulation in diabetic patients during the di et strengthens the hypothesis that fatty acids are associated with the upre gulation of uncoupling proteins during calorie restriction.