Genistein promotes insulin action through adenosine monophosphate-activated protein kinase activation and p70 ribosomal protein S6 kinase 1 inhibition in the skeletal muscle of mice fed a high energy diet

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• 作者：Elumalai Arunkumar ; Carani Venkatraman Anuradha
• 关键词：High fat&ndash ; high fructose diet ; Mice ; Insulin signaling ; Genistein ; Skeletal muscle ; AMP-activated protein kinase ; p70 ribosomal protein S6 kinase 1
• 刊名：Nutrition Research
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：32
• 期：8
• 页码：617-625
• 全文大小：1164 K

文摘

Genistein (GEN), a soy isoflavone, exerts insulin-sensitizing actions in animals; however, the underlying mechanisms have not been determined. Because GEN is a known activator of adenosine monophosphate-activated protein kinase (AMPK), we hypothesize that GEN activates insulin signaling through AMPK activation. To test this hypothesis, a high fat-high fructose diet (HFFD)-fed mice model of insulin resistance was administered GEN, and the insulin signaling pathway proteins in the skeletal muscle were examined. Hyperglycemia and hyperinsulinemia observed in HFFD-fed mice were significantly lowered by GEN. GEN increased insulin-stimulated tyrosine phosphorylation of insulin receptor-¦Â and insulin receptor substrate (IRS) 1 but down-regulated IRS-1 serine phosphorylation in the skeletal muscle of HFFD-fed mice. Furthermore, GEN treatment improved muscle IRS-1-associated phospatidylinositol-3 kinase expression, phosphorylation of Akt at Ser⁴⁷³, and translocation of glucose transporter subtype 4. Phosphorylation of AMPK at Thr¹⁷² and acetyl coenzyme A carboxylase (ACC) at Ser⁷⁹ was augmented, whereas phosphorylation of p70 ribosomal protein S6 kinase 1 at Thr³⁸⁹ was significantly decreased after GEN treatment in the skeletal muscle of HFFD-fed mice. These results suggest that GEN might improve insulin action in the skeletal muscle by targeting AMPK.