Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus

We examined the in vivo metabolic effects of vanadyl sulfate (VS) in non- insulin-dependent diabetes mellitus (NIDDM). Six NIDDM subjects treated with diet and/or sulfonylureas were examined at the end of three consecutive periods: placebo for 2 wk, VS (100 mg/d) for 3 wk, and placebo for 2 wk. Euglycemic hyperinsulinemic (30 mU/m² · min) clamps and oral glucose tolerance tests were performed at the end of each study period. Glycemic control at baseline was poor (fasting plasma glucose 210±19 mg/dl; HbA(1c) 9.6±0.6%) and improved after treatment (181±14 mg/dl [P < 0.05], 8.8±0.6%, [P < 0.002]); fasting and post-glucose tolerance test plasma insulin concentrations were unchanged. After VS, the glucose infusion rate during the clamp was increased (by ~ 88%, from 1.80 to 3.38 mg/kg · min, P < 0.0001). This improvement was due to both enhanced insulin-mediated stimulation of glucose uptake (rate of glucose disposal [R(d)], +0.89 mg/kg · min) and increased inhibition of HGP (-0.74 mg/kg · min) (P < 0.0001 for both). Increased insulin-stimulated glycogen synthesis (+0.74 mg/kg · min, P < 0.0003) accounted for > 80% of the increased R(d) after VS, and the improvement in insulin sensitivity was maintained after the second placebo period. The K(m) of skeletal muscle glycogen synthase was lowered by ~ 30% after VS treatment (P < 0.05). These results indicate that 3 wk of treatment with VS improves hepatic and peripheral insulin sensitivity in insulin- resistant NIDDM humans. These effects were sustained for up to 2 wk after discontinuation of VS.