We compared the effects of oral
vanadyl sulfate (100 mg/day) in moderately obese
NIDDM and nondiabetic subjects. Three-hour euglycemic-hyperinsulinemic (
insulin infusion 30 mU / m / min) clamps were performed after 2 weeks of placebo and 3 weeks of
vanadyl sulfate treatment in six nondiabetic control subjects (age 37 +/- 3 years; BMI 29.5 +/- 2.4 kg/m2 ) and seven
NIDDM subjects (age 53 +/- 2 years; BMI 28.7 +/-1.8 kg/m2).
Glucose turnover ([3-3 H]
glucose), glycolysis from plasma
glucose,
glycogen synthesis, and whole-body
carbohydrate and
lipid oxidation were evaluated. Decreases in fasting plasma
glucose (by approximately 1.7 mmol/l) and HbAlc (both P < 0.05) were observed in
NIDDM subjects during treatment; plasma
glucose was unchanged in control subjects. In the latter, the
glucose infusion rate (GIR) required to maintain euglycemia (40.1 +/- 5.7 and 38.1 +/- 4.8 micromol / kg fat-free mass FFM / min) and
glucose disposal (Rd) (41.7 +/- 5.7 and 38.9 +/-4.7 micromol / kg FFM / min were similar during placebo and
vanadyl sulfate administration, respectively. Hepatic
glucose output (HGO) was completely suppressed in both studies. In contrast, in
NIDDM subjects,
vanadyl sulfate increased GIR approximately 82% (17.3 +/- 4.7 to 30.9 +/- 2.7 micromol / kg FFM / min, P < 0.05); this improvement in
insulin sensitivity was due to both augmented stimulation of Rd (26.0 +/-4.0 vs. 33.6 +/- 2.22 micromol / kg FFM / min, P < 0.05) and enhanced suppression of HGO (7.7 +/- 3.1 vs. 1.3 +/- 0.9 micromol / kg FFM / min, P < 0.05). Increased
insulin-stimulated
glycogen synthesis accounted for >80% of the increased Rd with
vanadyl sulfate (P < 0.005), but plasma
glucose flux via glycolysis was unchanged. In
NIDDM subjects,
vanadyl sulfate was also associated with greater suppression of plasma
free fatty acids (FFAs) (P < 0.01) and
lipid oxidation (P < 0.05) during clamps. The reduction in HGO and increase in Rd were both highly correlated with the decline in plasma FFA concentrations during the clamp period (P < 0.001). In conclusion, small oral doses of
vanadyl sulfate do not alter
insulin sensitivity in nondiabetic subjects, but it does improve both hepatic and skeletal muscle
insulin sensitivity in
NIDDM subjects in part by enhancing
insulin's inhibitory effect on lipolysis. These data suggest that
vanadyl sulfate may improve a defect in
insulin signaling specific to
NIDDM.