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Partial hepatic resistance to IL-6-induced inflammation develops in type 2 diabetic mice, while the anti-inflammatory effect of AMPK is maintained

Author:
Cansby, Emmelie, Nerstedt, Annika, Amrutkar, Manoj, Durán, Esther Nuñez, Smith, Ulf, Mahlapuu, Margit
Source:
Molecular and Cellular Endocrinology 2014 v.393 pp. 143-151
ISSN:
0303-7207
Subject:
AMP-activated protein kinase, agonists, animal disease models, anti-inflammatory activity, gene expression, hepatocytes, high fat diet, inflammation, insulin resistance, interleukin-6, liver, metformin, mice, noninsulin-dependent diabetes mellitus
Abstract:
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.
Agid:
5522685