Early appearance of in vivo insulin resistance in adult streptozotocin-injected rats.

Hepatic glucose production and peripheral glucose utilisation were measured in vivo with the euglycaemic-hyperinsulinaemic clamp technique in rats rendered severely diabetics with streptozotocin (45 mg/kg) and in control rats. The rats were studied in the post-absorptive state while anaesthetised. The basal glucose production and glucose utilisation were significantly higher (p less than 0.05) in the diabetic rats as early as 1 day after the streptozotocin administration and remained elevated thereafter (P less than 0.01 on day 9 after streptozotocin). During the clamp studies, the suppression of glucose production by the liver induced by submaximal or maximal insulin levels was significantly less (p less than 0.05) effective in the diabetic rats as compared to control rats, as early as 1 day after streptozotocin. Following both submaximal or maximal hyperinsulinaemia, the glucose utilisation in the diabetic rats 1 day after streptozotocin was found to be not significantly different from the corresponding utilisation in the control rats. By contrast, in the diabetic rats 9 days after streptozotocin injection, glucose utilisation was significantly lower (P less than 0.01) following both a submaximal or a maximal hyperinsulinaemia as compared to control rats. Thus insulin deficiency and concomitant hyperglycaemia, as the consequences of streptozotocin administration in the adult rat, rapidly leads to the development of in vivo insulin resistance, first in the liver and later on in the peripheral tissues.