Calpain-10 gene and protein expression in human skeletal muscle: effect of acute lipid-induced insulin resistance and type 2 diabetes.

ABSTRACT

OBJECTIVE: Our objective was to investigate the effect of lipid-induced insulin resistance and type 2 diabetes on skeletal muscle calpain-10 mRNA and protein levels. RESEARCH DESIGN AND METHODS: In the first part of this study, 10 healthy subjects underwent hyperinsulinemic euglycemic (4.5 mmol/liter) clamps for 6 h with iv infusion of either saline or a 20% Intralipid emulsion (Fresenius Kabi AG, Bad Homburg, Germany). Skeletal muscle biopsies were taken before and after 3- and 6-h insulin infusion and analyzed for calpain-10 mRNA and protein expression. In the second part of the study, muscle samples obtained after an overnight fast in 10 long-standing, sedentary type 2 diabetes patients, 10 sedentary, weight-matched, normoglycemic controls, and 10 age-matched, endurance-trained cyclists were analyzed for calpain-10 mRNA and protein content. RESULTS: Intralipid infusion in healthy subjects reduced whole body glucose disposal by approximately 50% (P<0.001). Calpain-10 mRNA (P=0.01) but not protein content was reduced after 6-h insulin infusion in both the saline and Intralipid emulsion trials. Skeletal muscle calpain-10 mRNA and protein content did not differ between the type 2 diabetes patients and normoglycemic controls, but there was a strong trend for total calpain-10 protein to be greater in the endurance-trained athletes (P=0.06). CONCLUSIONS: These data indicate that skeletal muscle calpain-10 expression is not modified by insulin resistance per se and suggest that hyperinsulinemia and exercise training may modulate human skeletal muscle calpain-10 expression.