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Calpain-10 Gene and Protein Expression in Human Skeletal Muscle: Effect of Acute Lipid-Induced Insulin Resistance and Type 2 Diabetes

Centre for Integrated Systems Biology and Medicine (L.N., K.C., K.T.), School of Biomedical Sciences, Nottingham University Medical School, Queens Medical Centre, Nottingham, NG7 2UH, United Kingdom; Division of Nutritional Sciences (T.P., R.G.B.), School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, United Kingdom; Department of Medicine (H.Y., G.I.B.), University of Chicago, Chicago, Illinois 60637; and Department of Movement Sciences (M.M.A.L.P., L.J.C.v.L.), Maastricht University, 6211 KP Maastricht, The Netherlands

Address all correspondence and requests for reprints to: Dr. Kostas Tsintzas, School of Biomedical Sciences, Nottingham University Medical School, Queen’s Medical Centre, Nottingham, NG7 2UH, United Kingdom. E-mail: Kostas.Tsintzas{at}nottingham.ac.uk.

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.