Antidiabetic actions of arachidonic acid and zinc in genetically diabetic Goto-Kakizaki rats

In previous studies, we showed that feeding arachidonic acid (AA) supplemented with a fixed amount of zinc lowered blood glucose concentrations in the fed state and water intake in rats with streptozotocin-induced diabetes. The present study was designed to determine dose-dependent effects of AA supplemented with a fixed amount of zinc on fed blood glucose levels, water intake, and glucose tolerance in genetically type 2 diabetic Goto-Kakizaki (G-K) Wistar rats. In an acute study, 20 mg/kg AA plus 10 mg/kg zinc administered via gastric gavage significantly improved oral glucose tolerance in G-K rats when compared to rats given distilled water (DW) only. When rats were treated chronically (2 weeks) with increasing doses of AA in drinking water, fed blood glucose concentrations and water intake were maximally decreased with diets containing 20 or 30 mg/L AA plus 10 mg/L zinc. Three-hour average area-above-fasting glucose concentrations (TAFGC; index of oral glucose tolerance) in diabetic G-K rats treated with 10, 20, or 30 mg/L AA plus 10 mg/L zinc for 2 weeks were significantly decreased relative to DW-treated rats. The effect on TAFGC values was maintained for an additional 2 weeks after cessation of treatment. Plasma insulin levels significantly increased in rats treated with 20 mg/L AA only or 10 mg/L AA plus 10 mg/L zinc, but not in rats treated with 20 or 30 mg/L AA plus 10 mg/L zinc, which are the most effective doses for the improvement of clinical signs of diabetes in G-K rats. In in vitro assays, 0.2 mg/mL AA in the incubation media was optimal for glucose uptake in isolated soleus muscle slices. These results suggest that treatment of genetically diabetic G-K rats with AA plus zinc lowers blood glucose levels via improvement of insulin sensitivity. Copyright 2003, Elsevier Science (USA). All rights reserved.