In vivo insulin resistance in streptozotocin-diabetic rats — evidence for reversal following oral vanadate treatment

Summary Hepatic glucose production and peripheral glucose utilisation were measured in vivo with the euglycaemic-hyper-insulinaemic clamp technique in rats rendered severely diabetic 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<0.001) in diabetic rats 9 days after streptozotocin administration. During the clamp studies, suppression of glucose production by the liver induced by submaximal or maximal insulin levels was significantly less (p<0.01 and p<0.001 respectively) effective in diabetic rats as compared to control rats. Glucose utilisation was significantly lower following both submaximal (p<0.01) or maximal (p<0.001) hyperinsulinaemia as compared to control rats. Oral administration of vanadate (0.2mg/ml in drinking water) for a 20-day period in diabetic rats lowered their plasma glucose levels to normal near values within 4 days, normalised plasma insulin levels, and increased pancreatic insulin stores. The rate of glucose disappearance (K value) and in vivo glucose-induced insulin secretion as estimated during an i.v. glucose tolerance test were not significantly improved. In control rats, vanadate treatment did not significantly affect any of the above parameters. In vanadate treated diabetic rats, basal glucose production was normalised. Following submaximal or maximal hyperinsulinaemia, glucose production was suppressed normaly. Basal glucose utilisation was restored and returned to normal values during submaximal hyperinsulinaemia. However, during maximal hyperinsulinaemia, glucose utilisation still remained significantly lower (p<0.05) as compared to vanadate-treated control rats. Vanadate treatment in control rats did not affect significantly any of the above parameters. These results show an insulin-like effect of vanadate upon glucose metabolism in vivo in the liver and peripheral tissues of diabetic rats, leading to normalisation of glycaemia in the absence of any significant improvement of insulin secretion.