Effects of tungstate in neonatally streptozotocin-induced diabetic rats: mechanism leading to normalization of glycaemia

The effects of oral administration of tungstate to an animal model of non-insulin-dependent diabetes mellitus (NIDDM), the neonatally streptozotocin-induced diabetic rat was studied. Islet insulin content and beta-cell mass were lowered in these animals. Furthermore, the islets lost their ability to release insulin in response to an increase in glucose concentration. However, the hepatic glucose metabolism in these diabetic animals before the treatment was not significantly altered with regard to glycogen content, or glucokinase or glycogen phosphorylase activities compared with healthy animals. On the other hand, the activation state of glycogen synthase was higher although the total activity was unchanged. Moreover, a 20 % increase in the concentrations of liver glucose 6-phosphate compared to their healthy siblings was observed. Oral administration of tungstate for 15 days normalized glycaemia in these diabetic animals (4.6 vs 7.8 mmol/l). Tungstate administration was also able to normalize beta-cell insulin secretion in response to 16.7 mmol/l glucose stimulus, reaching values similar to those observed in healthy animals. Concomitantly, a partial recovery in the insulin content and in preproinsulin mRNA levels was found in the islets of treated animals, which was associated with an increase in the number of beta-cells in the pancreas (1.73 vs 0.86 %). The treatment did not change the liver parameters studied, except that it restored glucose 6-phosphate concentrations to healthy values. These data suggest that tungstate administration causes a normalization of glycaemia through the restoration of islet function. [Diabetologia (1997) 40: 143–149]