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

J Clin Invest. 1995 Jun;95(6):2501-9. doi: 10.1172/JCI117951.

Abstract

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; HbA1c 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 approximately 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 [Rd], +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 Rd after VS, and the improvement in insulin sensitivity was maintained after the second placebo period. The Km of skeletal muscle glycogen synthase was lowered by approximately 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Fatty Acids, Nonesterified / blood
  • Female
  • Glucose / metabolism
  • Glycogen Synthase / metabolism
  • Humans
  • Insulin / pharmacology*
  • Lactates / blood
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Muscles / enzymology
  • Phosphorylases / metabolism
  • Vanadium Compounds / administration & dosage*

Substances

  • Fatty Acids, Nonesterified
  • Insulin
  • Lactates
  • Vanadium Compounds
  • vanadyl sulfate
  • Phosphorylases
  • Glycogen Synthase
  • Glucose