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 expos ure on glucose tolerance of obese Zucker rats (fa/fa). DESIGN: Intrave nous glucose tolerance tests (2.4 mmol/kg, continuously from 0 to 30 m in) were performed in conscious Zucker rats exposed to a bolus-continu ous 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 exp eriments with saline infusion. RESULTS: Vanadate infusion improved glu cose tolerance and decreased insulin release, as shown by total areas under the curves (0-120 min: Glucose, min . mmol/l: control, 983 +/- 5 9 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, infusio n of selenate increased glucose induced insulin release during the fir st phase of the IVGTT (0-60 min, incremental area under the insulin cu rve: by 57% and 110% for low and high selenate infusion rate, respecti vely) and transiently improved glucose tolerance (0-60 min, decrease o f 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 expos ed rats without any adequate insulin secretory response to hyperglycem ia. CONCLUSION: The results demonstrate improved glucose tolerance and decreased plasma insulin concentration during acute vanadate exposure . Only a transient insulinotropic effect with improved glucose toleran ce is induced during acute selenate exposure, and is followed by progr essive development of hyperglycemia indicating selenate toxicity.