Characterization of insulin binding to skeletal muscle sarcolemma during the development of diabetes

The aim of the present study was to characterize insulin binding to isolated skeletal muscle sarcolemma during the development of experimental diabetes. Experimental diabetes with a persistent hyperglycemia of 363 ± 23 mg glucose/dl was induced in Sprague-Dawley rats by a single intravenous injection of streptozotocin (65 mg/kg body weight). Insulin binding to skeletal muscle sarcolemma was measured in control, 6-day, and 18-day diabetic rats, the latter group of which demonstrated signs of peripheral diabetic neuropathy and muscle wasting. Analysis of the binding data in an insulin concentration range of 7.5 × 10^-12 to 10^-8 m yielded curvilinear Scatchard plots. After 18 days, insulin binding increased in diabetic sarcolemma from 0.025 to 0.048 pmol/mg with no change in the dissociation constant (K_D = 1.69 × 10^-10 m) of the high-affinity segment of the Scatchard plots. Insulin binding was antagonized by insulin analogs in proportion to their biological potency (proinsulin > desoctapeptide ≫ glucagon).