Protective effects of epoxypukalide on pancreatic beta-cells and glucose metabolism in STZ-induced diabetic mice

摘要

Diabetes is a consequence of a decrease on functional -cell mass. We have recently demonstrated that epoxypukalide (Epoxy) is a natural compound with beneficial effects on primary cultures of rat islets. In this study, we extend our previous investigations to test the hypothesis that Epoxy protects -cells and improves glucose metabolism in STZ-induced diabetic mice.We used 3-months old male mice that were treated with Epoxy at 200 g/kg body weight. Glucose intolerance was induced by multiple intraperitoneal low-doses of streptozotocin (STZ) on 5 consecutive days. Glucose homeostasis was evaluated measuring plasma insulin levels and glucose tolerance. Histomorphometry was used to quantify the number of pancreatic -cells per islet. -cell proliferation was assessed by BrdU incorporation, and apoptosis by TUNEL staining. Epoxy treatment significantly improved glucose tolerance and plasma insulin levels. These metabolic changes were associated with increased -cell numbers, as a result of a two-fold increase in -cell proliferation and a 50% decrease in -cell death.Our results demonstrate that Epoxy improves whole-body glucose homeostasis by preventing pancreatic -cell death due to STZ-induced toxicity in STZ-treated mice.