Development of insulin resistance in normal dogs following alloxan-induced insulin deficiency

Insulin resistance was measured in 16 normal dogs by a method involving the continuous intravenous infusion of epinephrine, propranolol, glucose and insulin. With this approach, endogenous insulin secretin is inhibited, similar steady state levels of exogenous insulin are achieved in all doags, and the resultant steady state plasma glucose level provides a direct estimate of the ability of insulin to dispose of the infused glucose load. Thus, the higher the steady state plasma glucose level, the more the insulin resistance. Different amounts of alloxan were then administered to these dogs in order to produce insulin deficiency of varying degrees. Insulin resistance was then measured again in each dog. The results indicated that insulin resistance did not develop in dogs with only a moderate degree of insulin deficiency (fasting plasma glucose levels less than 150 mg/100 ml). On the other hand, a significant degree of insulin resistance developed in dogs with severe insulin deficiency (fasting plasma glucose greater than 150 mg/100 ml). Furthermore, the insulin resistance that developed in dogs with severe insulin deficiency could be returned to normal with insulin replacement for one week. These results indicate that insulin resistance can occur as a secondary manifestation of insulin deficiency.