Evaluation of the Role of the Sympathetic Nervous System in the Glucoregulatory Response to Insulin-Induced Hypoglycemia in the Rat

Abstract
The influence of the i.v. injection of insulin (50 mU [milliunits]) on the rates of hepatic glucose production (Ra) and peripheral uptake (Rd) was studied in normal and adreno-demedullated, reserpinized rats by using the primed constant infusion of [2-3H]glucose. In normal rats plasma glucose levels fell promptly after insulin injection, reaching the nadir of 40 mg/100 ml at 20 min and then returned slowly to values very close to the baseline within 60 min. Glucose production by the liver, after a rapid and moderate decrease, showed a significant increase which persisted throughout the experimental period. The modifications of Rd induced by the administration of insulin were grossly opposite to those of Ra. In demedullated reserpine-treated rats insulin-induced hypoglycemia was more pronounced than in controls, without any clear tendency toward recovery until 40 min after the injection of insulin. In these experiments, Ra declined progressively following insulin reaching much lower levels than in the controls, and did not show any secondary positive wave. Plasma glucagon levels increased markedly in response to hypoglycemia and did not show any appreciable difference between normal and demedullated reserpine-treated rats. The integrity of the sympathetic nervous system is essential for an efficient homeostatic response to insulin-induced hypoglycemia. On the other hand, glucagon hypersecretion by itself does not seem able to counteract adequately the restraining effect on glucose production induced by the administration of a pharmacologic dose of insulin. Although this conclusion may apply only to the rat, the current findings stimulate further investigation on the role of the sympathetic system in the maintenance of glucose homeostasis in other animal species.

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