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

Abstract
Diabetes is a consequence of a decrease on functional β-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 β-cells and improves glucose metabolism in STZ-induced diabetic mice. We used 3-months old male mice that were treated with Epoxy at 200 μg/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 β-cells per islet. β-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 β-cell numbers, as a result of a two-fold increase in β-cell proliferation and a 50% decrease in β-cell death. Our results demonstrate that Epoxy improves whole-body glucose homeostasis by preventing pancreatic β-cell death due to STZ-induced toxicity in STZ-treated mice.
AuthorsJose F López-Acosta, Pablo Villa-Pérez, Cristina M Fernández-Díaz, Daniel de Luis Román, Ana R Díaz-Marrero, Mercedes Cueto, Germán Perdomo, Irene Cózar-Castellano
JournalIslets (Islets) Vol. 7 Issue 2 Pg. e1078053 ( 2015) ISSN: 1938-2022 [Electronic] United States
PMID26406478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hypoglycemic Agents
  • Insulin
  • Lactones
  • 11,12-epoxypukalide
  • Glucose
Topics
  • Animals
  • Diabetes Mellitus, Experimental (drug therapy)
  • Glucose (metabolism)
  • Glucose Tolerance Test
  • Hypoglycemic Agents (pharmacology)
  • Insulin (blood)
  • Insulin-Secreting Cells (drug effects)
  • Lactones (pharmacology)
  • Male
  • Mice

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