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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

IL-6

AMPK

Inflammation

Liver

Type 2 diabetes

ACTIVATED PROTEIN-KINASE

ACUTE-PHASE RESPONSE

INDUCED

GLUCOSE-INTOLERANCE

ADULT-RAT HEPATOCYTES

HUMAN SKELETAL-MUSCLE

STIMULATORY FACTOR-II

TUMOR-NECROSIS-FACTOR

FATTY-ACID OXIDATION

C-REACTIVE PROTEIN

INSULIN-RESISTANCE

Cell Biology

Endocrinology & Metabolism

GA T

1989

CELL

V58

P573

GA T

1987

JOURNAL OF EXPERIMENTAL MEDICINE

V166

P967

EWARD AR

1985

MOLECULAR PHARMACOLOGY

V27

P125

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