期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 393, 期 1-2, 页码 143-151出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2014.06.014
关键词
IL-6; AMPK; Inflammation; Liver; Type 2 diabetes
资金
- Swedish Research Council
- European Foundation for the Study of Diabetes/Lilly research grant
- European Foundation for the Study of Diabetes
- Novo Nordisk Partnership for Diabetes Research in Europe
- Novo Nordisk Foundation
- Diabetes Wellness Network Sweden
- Ake Wiberg Foundation
- Diabetesfonden
- Adlerbert Research Foundation
- M. Bergvall Foundation
- Royal Society of Arts and Sciences Foundation
Interleukin-6 (IL-6) induces hepatic inflammation and insulin resistance, and therapeutic strategies to counteract the IL-6 action in liver are of high interest. In this study, we demonstrate that acute treatment with AMP-activated protein kinase (AMPK) agonists AICAR and metformin efficiently repressed IL-6-induced hepatic proinflammatory gene expression and activation of STAT3 in a mouse model of diet-induced type 2 diabetes, bringing it back to basal nonstimulated level. Surprisingly, the inflammatory response in liver induced by IL-6 administration in vivo was markedly blunted in the mice fed a high-fat diet, compared to lean chow-fed controls, while this difference was not replicated in vitro in primary hepatocytes derived from these two groups of mice. In summary, our work reveals that partial hepatic IL-6 resistance develops in the mouse model of type 2 diabetes, while the anti-inflammatory action of AMPK is maintained. Systemic factors, rather than differences in intracellular IL-6 receptor signaling, are likely mediating the relative impairment in IL-6 effect. (C) 2014 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