Diabetes, Vol 39, Issue 11 1326-1332, Copyright © 1990 by American Diabetes Association
Marked improvement of glucose homeostasis in diabetic ob/ob mice given oral vanadate
SM Brichard, CJ Bailey and JC Henquin
Diabetology and Nutrition Unit, University of Louvain School of Medicine, Brussels, Belgium.
The trace element vanadium exerts insulinlike effects in vitro and
decreases hyperglycemia in insulin-deficient animals. This study examined
whether vanadate can improve glucose homeostasis in genetically obese
hyperglycemic insulin-resistant ob/ob mice, which present metabolic
abnormalities similar to those of human non-insulin-dependent diabetes.
Sodium orthovanadate (0.3 mg/ml) was administered for 7 wk in H2O. Vanadate
treatment induced a fall in fed and fasted plasma glucose and insulin
levels and improved tolerance to oral glucose; the stimulated glucose area
was decreased by 65%, and an early peak of insulin secretion was restored.
During an intravenous glucose tolerance test, the glucose disappearance
rate was twofold higher in vanadate-treated mice, and the reappearance of a
significant insulin response was also observed. Moreover, vanadate produced
a twofold increase in hepatic glycogen content and prevented the exhaustion
of pancreatic insulin stores. The hypoglycemic response to exogenous
insulin was similar in control and treated mice. In vitro experiments
showed that basal glucose oxidation by hemidiaphragms was 32% higher in
vanadate-treated mice than in controls, although stimulation by insulin was
similar in both groups. In conclusion, oral vanadate caused a marked and
sustained improvement of glucose homeostasis in diabetic insulin-resistant
mice by exerting an insulinlike effect on peripheral tissues and apparently
preventing the exhaustion of pancreatic insulin stores.