Inhibition effect of dehydroascorbic acid on insulin secretion from mouse pancreatic islets.

Intravenous doses of 200 mg/kg dehydroascorbic acid (DHA) 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^?3m). 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 to 4.0 mg/dl of DHA causes a leakage of insulin. Similarly, islets isolated from mice which had been treated with 300 mg/kg DHA iv exhibited increased insulin release in the presence of only 60 mg/dl glucose. Intravenous 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 results show that the pancreatic effects of DHA are similar to those of the diabetogen, alloxan.