ORAL VANADATE DECREASES MUSCLE INSULIN RESISTANCE IN OBESE FA/FA RATS

Oral vanadate has been reported as improving glucose homeostasis in genetically obese and hyperinsulinaemic fa/fa rats. It has also been shown that these beneficial effects could not be ascribed to the decrease in body weight induced by thc treatment, or to changes in insulin counterregulatory hormones. The present study examined therefor whether the effects of vanadate could be attributed to a direct correction of the severe insulin resistance of these animals. fa/fa Rats chronically treated with vanadate were compared to both control rats fed ad libitum and pair-fed rats. The three groups were studied in the basal state and during euglycaemic hyperinsulinaemic clamps. Slightly lower plasma glucose levels were always maintained in vanadate-treated rats in conjunction with markedly lower plasma insulin levels either during basal or clamp studies. During thc clamp, the glucose infusion rate required to maintain glycaemia at basal values was consistently higher in vanadate-treated rats than in the other two groups. Experiments using [6-H-3]glucose as tracer showed that this was not due to a greater inhibition of hepatic glucose production by insulin, but corresponded to a larger increment in peripheral glucose disposal The stimulation of overall glucose metabolic clearance induced by insulin was 129% and 41% higher in vanadate-treated than in control and pair-fed rats respectively. Similar experiments with 2-deoxy-[1-H-3]glucose as tracer showed that the larger increase in insulin-mediated glucose clearance occurred in various types of muscle. The action of insulin was particularly impressive on the cardiac muscle of vanadate-treated rats. In conclusion, the beneficial effects of vanadate on glucose homeostasis in obese hyperinsulinaemic fa/fa rats involve a sustained improvement of the impaired sensitivity to insulin in muscle.