Insulin-like actions of tungstate in diabetic rats. Normalization of hepatic glucose metabolism.

Oral administration of tungstate for 15 days normalized glycemia in streptozotocin-induced diabetic rats. Simultaneously, the alterations in hepatic glucose metabolism due to diabetes were almost completely counteracted by this treatment. Thus, 6-phosphofructo-2-kinase, L-pyruvate kinase, and glycogen phosphorylase alpha activities reached levels similar to those observed in healthy animals. Hepatic levels of fructose 2,6-bisphosphate and glycogen also recovered. However, the recovery of glucokinase activity and hepatic levels of glucose 6-phosphate was only partial. The total activity of glycogen synthase increased, although the activation state was not recovered. Moreover, mRNA levels of hepatic glucokinase, glycogen phosphorylase, and phosphoenolpyruvate carboxykinase were also normalized. Tungstate administration in healthy animals also affected all these parameters, although to a much lesser extent. All these effects were similar to those previously reported for vanadate, suggesting a common mechanism of action in vivo.