Ebselen Treatment Prevents Islet Apoptosis, Maintains Intranuclear Pdx-1 and MafA Levels, and Preserves β-Cell Mass and Function in ZDF Rats

• DOI: 10.2337/db13-0357
• Publication Date: 2013-06-26T03:27:04Z
• Authors: Jana Mahadevan; Susan Parazzoli; Elizabeth Oseid; Ann V. Hertzel; David A. Bernlohr; Sara N. Vallerie; Chang-qin Liu; Melissa Lopez; Jamie S. Harmon; R. Paul Robertson
• Keywords: Ebselen

We reported earlier that β-cell–specific overexpression of glutathione peroxidase (GPx)-1 significantly ameliorated hyperglycemia in diabetic db/db mice and prevented glucotoxicity-induced deterioration β-cell mass function. have now ascertained whether early treatment Zucker fatty (ZDF) rats with ebselen, an oral GPx mimetic, will prevent deterioration. No other antihyperglycemic was given. Ebselen fasting hyperglycemia, sustained nonfasting insulin levels, lowered glucose HbA1c levels no effects on body weight. doubled mass, apoptosis, expression oxidative stress markers, enhanced intranuclear localization pancreatic duodenal homeobox (Pdx)-1 v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA), two critical transcription factors. Minimal replication observed both groups. These findings indicate prevention is the mechanism whereby ebselen prevents apoptosis preserves Pdx-1 MafA, which, turn, a likely explanation for beneficial Since antioxidant currently used clinical trials, it novel therapeutic candidate to ameliorate further function humans undergoing onset type 2 diabetes.