HYPOXIC EFFECT OF EXOGENOUS INSULIN ON NORMAL AND DIABETIC PERIPHERAL-NERVE

Insulin administration can cause or worsen experimental and human diab etic neuropathy (''insulin neuritis''). In this study, we tested the h ypothesis that insulin administration impairs tissue oxygenation. We i nfused insulin under nonhypoglycemic conditions and evaluated its effe ct on endoneurial oxygen tension, nerve blood flow, and the oxyhemoglo bin dissociation curve of peripheral nerve in normal and diabetic rats . Intravenous insulin infusion resulted in a dose-dependent reduction in endoneurial oxygen tension in normal nerves (from 26% at 0.04 U/kg insulin to 55% at 32 U/kg). The nerves of rats with streptozotocin-ind uced diabetes were resistant, but with control of hyperglycemia this s usceptibility to the endoneurial hypoxic effect of insulin returned. T he reduction in endoneurial oxygen tension regressed with glycosylated hemoglobin (Y = 53.8 - 2.7X, where Y = %reduction in endoneurial oxyg en tension and X = Hb(A1); 7. = 0.87; P = < 0.001). Diabetes or insuli n administration resulted in only minimal and physiologically insignif icant alterations in the oxygen dissociation curve and 2,3-diphosphogl ycerate of sciatic nerve. Instead, insulin administration resulted in a reduction in nerve nutritive blood flow and an increase in arteriove nous shunt flow. When the latter was eliminated by the closure of arte riovenous shunts (infusion of 5-hydroxytryptamine, endoneurial oxygen reverted to normal. These findings indicate a deleterious vasoactive e ffect of insulin and may explain the development of insulin neuritis.