Selective reduction of creatine kinase subunit mRNAs in striated muscle of diabetic rats.

Abstract

Creatine kinase (CK) is important for energy transfer and is composed of mitochondrial (mitCK), muscle (MCK), and brain (BCK) subunits, each being the product of separate nuclear genes. The concentrations of MCK and BCK mRNAs have been shown to decrease in streptozotocin-hypoinsulinemic rat hearts, and in this report, we examined in detail the diabetic effect on CK gene expression in cardiac muscle and in two types of skeletal muscle. The level of sarcomeric mitCK mRNA was not altered in the diabetic myocardium, but was reduced by 86 and 67% in diabetic slow-twitch soleus muscle and fast-twitch extensor digitorum longus (EDL) muscle, respectively. MCK mRNA was also lowered in diabetic soleus muscle by 56%, while it remained at control levels in diabetic EDL. In both skeletal muscles, at either state, BCK mRNA was not detectable. There was a 33% decrease in total CK activity in diabetic cardiac and soleus muscle, but not in EDL. Diabetes thus exerts a widespread, muscle type-dependent adverse effect on CK expression that we found to be insulin therapy revertible. This study adds to our understanding of defective energy transduction in diabetic muscle.