The effect of constant, controlled hyperinsulinemia on in vivo and in vitro insulin responsiveness has been investigated in rats that have received insulin infusions through chronically implanted jugular vein catheters. Constant rates of insulin infusion during days 1–4 resulted in stable plasma insulin concentrations. The plasma glucoseinitially fell from 122 ± 3 to 53 ± 4 mg/dl. While the infusion rate was maintained constant,the plasma glucose continued to fall over the subsequent days so that on day 4 the plasma glucose, 40 ± 2 mg/dl, was significantly lower than that in the same animals on day 1 (P < 0.02). Subsequently, the rate of insulin infusion was decreased to maintain the plasma glucose level in the 35—40 mg/dl range. Plasma catecholamine levels were high in insulin-infused rats. On the eighth day an in vivo insulin tolerance test (0.5 U/kg) was performed. Insulin-infused rats responded with a hypoglycemia that was both more pronounced and longer sustained than in salineinfused controls.

Insulin responsiveness in vitro has been measured in isolated adipocytes. Adipocytes from epididymal fat pads were of similar size in the two groups of animals. Glucose uptake by adipocytes from insulin-infused rats was similar to that of controls under basal (zero insulin) conditions, but showed an increase in the maximum response to insulin. Glucose incorporation into total lipid and fatty acid was greater in adipocytes from insulin-infused rats than in controls under both basal (zero insulin) and insulin-stimulated conditions. Activities of the lipogenic enzymes acetyl CoA carboxylase and fatty acid synthetase were markedly increased in epididymal fat pads of insulin-infused rats.

Thus, insulin infusion for a period of 8 days did notresult in reduced insulin action in vivo; on the contrary, an apparent increase in the hypoglycemic effect of insulin was observed. In vitro, the maximum effect of insulin on glucose uptake and lipogenesis in the isolated adipocyte was markedly increased after in vivo insulin infusion.

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