Ebselen treatment prevents islet apoptosis, maintains intranuclear Pdx-1 and MafA levels, and preserves β-cell mass and function in ZDF rats.
Ebselen treatment prevents islet apoptosis, maintains intranuclear Pdx-1 and MafA levels, and preserves β-cell mass and function in ZDF rats.
复制标题
DOI：
10.2337/db13-0357
复制
发表时间：
2013-10
期刊：
影响因子：
7.7
通讯作者：
Robertson RP
中科院分区：
文献类型：
--
作者：
Mahadevan J;Parazzoli S;Oseid E;Hertzel AV;Bernlohr DA;Vallerie SN;Liu CQ;Lopez M;Harmon JS;Robertson RP
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 of β-cell mass and function. We have now ascertained whether early treatment of Zucker diabetic fatty (ZDF) rats with ebselen, an oral GPx mimetic, will prevent β-cell deterioration. No other antihyperglycemic treatment was given. Ebselen ameliorated fasting hyperglycemia, sustained nonfasting insulin levels, lowered nonfasting glucose levels, and lowered HbA1c levels with no effects on body weight. Ebselen doubled β-cell mass, prevented apoptosis, prevented expression of oxidative stress markers, and enhanced intranuclear localization of pancreatic and duodenal homeobox (Pdx)-1 and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA), two critical insulin transcription factors. Minimal β-cell replication was observed in both groups. These findings indicate that prevention of oxidative stress is the mechanism whereby ebselen prevents apoptosis and preserves intranuclear Pdx-1 and MafA, which, in turn, is a likely explanation for the beneficial effects of ebselen on β-cell mass and function. Since ebselen is an oral antioxidant currently used in clinical trials, it is a novel therapeutic candidate to ameliorate fasting hyperglycemia and further deterioration of β-cell mass and function in humans undergoing the onset of type 2 diabetes.
登录
查看更多内容
影响因子：
7.4
作者：
Lenzen, S;Drinkgern, J;Tiedge, M
通讯作者：
Tiedge, M
影响因子：
4.8
作者：
Harmon, Jamie S.;Bogdani, Marika;Robertson, R. Paul
通讯作者：
Robertson, R. Paul
影响因子：
7.7
作者：
Kawamori, D;Kajimoto, Y;Hori, M
通讯作者：
Hori, M
DOI：
10.1152/ajpendo.00252.2004
发表时间：
2005-04-01
影响因子：
5.1
作者：
Brissova, M;Blaha, M;Powers, AC
通讯作者：
Powers, AC
影响因子：
20.1
作者：
Brodsky, SV;Gealekman, O;Goligorsky, MS
通讯作者：
Goligorsky, MS