The Effects of Biosynthetic Human Proinsulin on Carbohydrate Metabolism in Non-Insulin-Dependent Diabetes Mellitus

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Abstract
We compared the glucose-lowering effect of proinsulin, the precursor molecule of insulin, with that of insulin itself. In patients with non-insulin-dependent diabetes mellitus (NIDDM) in whom proinsulin (0.2 U per kilogram of body weight) was subcutaneously injected at 9 a.m., fasting glucose levels (247±22 mg per deciliter [±SEM]) became normal within six hours and elevated rates of hepatic glucose output were lowered. The response to regular insulin (0.2 U per kilogram) was of similar magnitude but faster. Glucose clearance was stimulated less by proinsulin, reflecting its preferential action in suppressing glucose output. Hypoglycemia occurred in five of nine insulin-treated patients, but in only one of nine proinsulin-treated patients.