Characterization of rat skeletal muscle sarcolemma during the development of diabetes

Peripheral neuropathy accompanied by decreased axonal conduction velocity is a common complication of diabetes. Skeletal muscle weakness and wasting also occur in the severe, uncontrolled form of the disease. For these reasons, it has been hypothesized that diabetes may cause denervation-like changes in skeletal muscle. In the present study, sarcolemmal membranes were characterized in control, early, and late stages of streptozotocin diabetes. After 3 weeks, axonal conduction velocities decreased 25% and muscle weight decreased 50% in diabetic rats. No significant changes were observed in Na⁺,K⁺ (Mg²⁺)-ATPase or adenylate cyclase activities during diabetes. The number of β-adrenergic receptor sites, however, increased from 0.39 pmol/mg in control sarcolemma to 0.46 and 0.58 pmol/mg after 6 and 18 days of diabetes, respectively, with no change in the affinity constant. Membrane phospholipid and polypeptide compositions were unaltered during diabetes, whereas the cholesterol content increased 23% in 18-day diabetic sarcolemma. There was also a 2.5-fold increase in glycosylation of a 72,000-molecular weight glycopeptide after 18 days of diabetes. Previous studies showed that denervation results in a decrease in sodium fluoride- and catecholamine-stimulated adenylate cyclase activities, an increase in Na⁺,K⁺ (Mg²⁺)-ATPase activity, no change in the number or affinity of β-adrenergic receptor sites, and no change in membrane glycosylation (1977. Exp. Neurol. 56: 102-114). These findings demonstrate that diabetic and denervated skeletal muscle sarcolemma are distinctly different with respect to a number of their biochemical properties.