Long term improvement of glucose homeostasis by vanadate treatment in diabetic rats

The trace element vanadium (V) exerts insulin-like effects in vitro. The present study examined its effects on glucose homeostasis in rats made diabetic by streptozotocin. Na3VO4 (0.2 or 0.5 mg/ml) was administered ad libitum in drinking water. Fed plasma glucose levels (approximately 26 mmol/liter) fell by 30% and 56% after 5 days of treatment with the low (VO.2) and high (VO.5) concentrations of vanadate, respectively. This decrease was not due to a rise in peripheral insulin levels and persisted for more than 2 months. Daily glucosuria was decreased by 60% and 85% in VO.2 and VO.5 rats, respectively. Tolerance of the rats to oral or iv glucose was also considerably improved by vanadate; integrated glucose responses were about 55% and 75% lower in VO.2 and VO.5 rats than in controls, and the differences were not due to restoration of insulin release. Compared to nondiabetic rats, pancreatic insulin reserves amounted to 1% in untreated rats, 3% in VO.2 rats, and 6% in VO.5 rats after 9 weeks of treatment. Liver, but not muscle, glycogen was increased by vanadate. Despite improvement of their diabetic state, vanadate-treated rats did not gain more weight than untreated rats. Their food intake (corrected for urinary glucose losses) was decreased by about 25%. No signs of altered kidney or liver function were observed in rats receiving vanadate. In conclusion, vanadate markedly improves glucose homeostasis in streptozotocin-diabetic rats by an insulin-like mechanism, but does not reproduce the anabolic effects of the hormone.