期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 290, 期 2, 页码 E251-E257出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00096.2005
关键词
lipids; peroxisome proliferator-activated receptor-gamma; thiazolidinedione; Zucker rats; adenosine monophosphate-activated protein kinase-alpha 2
Rosiglitazone ( RSG) is an insulin-sensitizing thiazolidinedione ( TZD) that exerts peroxisome proliferator-activated receptor-gamma ( PPAR gamma)-dependent and -independent effects. We tested the hypothesis that part of the insulin-sensitizing effect of RSG is mediated through the action of AMP-activated protein kinase ( AMPK). First, we determined the effect of acute ( 30 - 60 min) incubation of L6 myotubes with RSG on AMPK regulation and palmitate oxidation. Compared with control ( DMSO), 200 mu M RSG increased ( P < 0.05) AMPK alpha 1 activity and phosphorylation of AMPK ( Thr(172)). In addition, acetyl-CoA carboxylase ( Ser(218)) phosphorylation and palmitate oxidation were increased ( P < 0.05) in these cells. To investigate the effects of chronic RSG treatment on AMPK regulation in skeletal muscle in vivo, obese Zucker rats were randomly allocated into two experimental groups: control and RSG. Lean Zucker rats were treated with vehicle and acted as a control group for obese Zucker rats. Rats were dosed daily for 6 wk with either vehicle ( 0.5% carboxymethylcellulose, 100 mu l/100 g body mass), or 3 mg/kg RSG. AMPK alpha 1 activity was similar in muscle from lean and obese animals and was unaffected by RSG treatment. AMPK alpha 2 activity was similar to 25% lower in obese vs. lean animals ( P < 0.05) but was normalized to control values after RSG treatment. ACC phosphorylation was decreased with obesity ( P < 0.05) but restored to the level of lean controls with RSG treatment. Our data demonstrate that RSG restores AMPK signaling in skeletal muscle of insulin-resistant obese Zucker rats.
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