Calcium pump activity of sarcoplasmic reticulum in diabetic rat skeletal muscle

Ca2+ pump activity of skeletal muscle microsomes containing fragments of sarcoplasmic reticulum was examined in rats 8 wk after the induction of chronic diabetes by an intravenous injection of streptozotocin (65 mg/kg). In comparison with the control values, both ATP-dependent Ca2+ uptake and Ca2+-stimulated ATPase activities were increased in the microsomal fraction from diabetic rats. These changes were seen as early as 7 days after streptozotocin injection and were apparent at various times of incubation (1-10 min) as well as at different concentrations of free Ca2+ (10(-7)-5 X 10(-5) M Ca2+). Insulin administration to diabetic animals for 2 wk reversed Ca2+ uptake and ATPase activities to control levels. The increase in microsomal ATPase activity of the diabetic preparation due to cAMP-dependent protein kinase or calmodulin was greater than in the control microsomes and the depression by a specific inhibitor of protein kinase, but not of calmodulin, was greater in diabetic muscle. The enhanced Ca2+ pump activity was associated with altered phospholipid composition and protein profile of the diabetic preparations. The rate of Ca2+ release from microsomal vesicles was unaffected by the diabetic condition. Isometric contractile force development as well as positive dF/dt and negative dF/dt of the skeletal muscle from diabetic animals were higher at different pulse strengths (0.5-100 V) and at different Ca2+ concentrations (0.25-2.5 mM). These results suggest that diabetes is associated with enhanced sarcoplasmic reticular Ca2+ pump activity, and this may account for the hyperfunction of skeletal muscle in this disease.