INHIBITORY EFFECT OF DEHYDROASCORBIC ACID ON INSULIN-SECRETION FROM MOUSE PANCREATIC-ISLETS

I.v. doses of 200 mg/kg dehydroascorbic acid (DHA [an ascorbic acid metabolite]) produced hyperglycemia, hypoinsulinemia and decreased glucose tolerance in mice. This effect of DHA is mediated, at least in part, through a direct inhibition of pancreatic insulin release. Exposure of isolated pancreatic islets to a concentration of 2.0 mg/dl DHA reduces the responsiveness of the islets to both glucose (300 mg/dl) and tolbutamide (6 .+-. 10-3 M). Exposure of isolated islets to DHA in a high concentration of D-glucose (300 mg/dl) partially protected them against the inhibitory effect of DHA. Exposure of islets of 4.0 mg/dl of DHA causes a leakage of insulin. Islets isolated from mice which were treated with 300 mg/kg DHA i.v. exhibited increased insulin release in the presence of only 60 mg/dl glucose. I.v. administration of either 200 or 300 mg/kg DHA prior to islet isolation results in increased insulin secretion in response to 300 mg/dl glucose. The pancreatic effects of DHA are similar to the diabetogen, alloxan.