Long Term Improvement of Glucose Homeostasis by Vanadate in Obese Hyperinsulinemic fa/fa Rats*

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Abstract
The trace element vanadium (V) exerts insulin-like effects in vitro and lowers blood glucose in streptozotocin-diabetic rats. The present study examined whether V can also improve glucose homeostasis in genetically obese, insulin-resistant rats. Na3VO4 was administered for 3 months in water and food to Zucker fa/fa rats. Since these V rats reduced their food intake by about 30% compared to controls (C), one group of untreated rats was pair-fed (P-F) with V rats. In the fed state, the insulin/glucose ratio was lower in V rats than in P-F or C rats, merely because of a decrease (.apprx. -50%) in plasma insulin levels. Tolerance to oral glucose was improved in V rats only; the integrated glucose response was 30% lower than that in P-F or C rats. Insulin levels were also lower in V rats, but the integrated response was not consistently decreased. During an iv glucose tolerance test, the glucose disappearance rate was 50% higher in V rats than in the other two groups. An iv arginine test clearly showed that B-cell responsiveness was not increased in V rats. Insulin sensitivity, assessed by insulin-induced hypoglycemia, was similar in V and P-F rats and slightly better than that in C rats. In conclusion, oral vanadate produces a sustained improvement of glucose homeostasis by an insulin-like, largely body weight-independent mechanism in genetically insulin-resistant rats.