IMPROVED GLUCOSE-TOLERANCE BY ACUTE VANADATE BUT NOT BY SELENATE EXPOSURE IN GENETICALLY-OBESE RATS (FA/FA)

OBJECTIVE: To describe the impact of acute vanadate and selenate exposure on glucose tolerance of obese Zucker rats (fa/fa). DESIGN: Intravenous glucose tolerance tests (2.4 mmol/kg, continuously from 0 to 30 min) were performed in conscious Zucker rats exposed to a bolus-continuous infusion of sodium vanadate (2.45 mu mol/h) or sodium selenate (0.90 and 2.45 mu mol/h) and were compared to intraindividual control experiments with saline infusion. RESULTS: Vanadate infusion improved glucose tolerance and decreased insulin release, as shown by total areas under the curves (0-120 min: Glucose, min . mmol/l: control, 983 +/- 59 vs vanadate, 915 +/- 54, P < 0.02; Insulin min nmol/l: control, 117.5 +/- 19.9 vs vanadate, 88.5 +/- 26.2, P < 0.01). In contrast, infusion of selenate increased glucose induced insulin release during the first phase of the IVGTT (0-60 min, incremental area under the insulin curve: by 57% and 110% for low and high selenate infusion rate, respectively) and transiently improved glucose tolerance (0-60 min, decrease of incremental area under the glucose curve: 31% and 28%, respectively). That effect of selenate was lost with progression of the experiment during the second hour of the IVGTT, when plasma glucose continued to decline slowly in control experiments, but increased in selenate exposed rats without any adequate insulin secretory response to hyperglycemia. CONCLUSION: The results demonstrate improved glucose tolerance and decreased plasma insulin concentration during acute vanadate exposure. Only a transient insulinotropic effect with improved glucose tolerance is induced during acute selenate exposure, and is followed by progressive development of hyperglycemia indicating selenate toxicity.