期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 323, 期 2, 页码 246-255出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2010.02.041
关键词
Succinobucol; Probucol; Cytokines; Inflammation; Antioxidant; Oxidative stress; Anti-inflammatory; K-ATP-channel; Glucose sensitivity; Glucokinase; Calcium; Biphasic; Insulin; Beta-cell; Beta cells; ER stress
资金
- AtheroGenics Inc.
- NIH [1K01 DK081621, RO1 DK 55240]
- Mouse Metabolic Phenotyping Center (MMPC) [07-MCG-22]
- UVA DERC [DK063609]
The antioxidant and anti-inflammatory compound AGI-1067 (succinobucol) has potential as an oral anti-diabetic agent. AGI-1067 reduces H(b)A1c, improves fasting plasma glucose, and reduces new-onset diabetes. We investigated AGI-1067 for possible effects on mouse pancreatic islets in vitro. Pretreatment with 10 mu M AGI-1067 increased glucose-stimulated insulin secretion (11 mM) without affecting secretion in basal (3 mM) glucose. AGI-1067 enhanced the intracellular calcium response to glucose stimulation in 7 mM and 11 mM glucose, but had no effect in .28 mM or basal glucose. AGI-1067-pretreated islets also showed enhanced calcium responses to methyl pyruvate and alpha-ketoisocaproate at low doses, but not high doses. The AGI-1067-mediated effects on glucose-stimulated calcium were maintained during continuous diazoxide exposure, suggesting effects on the K-ATP-channel-independent pathway. AGI-1067 also reduced cytokine-induced islet cell death and expression of iNOS, a key component in cytokine signaling. This is the first report of direct stimulatory and protective effects of a first-in-class potential anti-diabetic agent on pancreatic islets. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据