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 (KD = 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).
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