title: AICAR enhances insulin signaling via downregulation of miR-29.
abstract: As an activator of AMPK, the effect of AICAR on insulin signaling has not been investigated extensively. PI3K-Akt is a critical node involved in the insulin signaling pathway. We observed that concomitant with the activation of AMPK by AICAR, the protein level of PI3K p85α and the insulin-induced phosphorylation of Akt were enhanced in mouse primary hepatocytes. Previously, we identified a group of AMPK-regulated miRNAs in hepatocytes. It is not clear whether miRNAs are related to the regulation of insulin signaling by AMPK. Here, we confirmed the negative regulation of miR-29 family members by AICAR treatment in mouse primary hepatocytes. Our results indicated that p85α is a direct target of miR-29 and is negatively regulated by miR-29b in hepatocytes. In agreement with the findings in vitro, we found that the expression of miR-29 and the protein levels of p85α were inversely correlated in the liver of fasted mice. Overexpression of miR-29b reduced the insulin-induced phosphorylation of Akt in hepatocytes, suggesting that miR-29 could serve as a negative regulator of insulin signaling. Furthermore, we found that overexpression of miR-29 could attenuate the effect of AICAR on p85α expression. Taken together, our results indicated that activation of AMPK may enhance insulin signaling via downregulation of miR-29.
authors.affiliation: a 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 66 Tong-an Road, Tianjin 300070, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: b Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ye
authors.affiliation: b Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: a 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 66 Tong-an Road, Tianjin 300070, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: a 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 66 Tong-an Road, Tianjin 300070, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: a 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 66 Tong-an Road, Tianjin 300070, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: b Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.|c Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
keywords: AMP-activated protein kinase; insulin signaling pathway; micro ARN-29; microRNA-29; p85α; phospho-inositide 3-kinase; phosphoinositide 3-kinase; protéine kinase activée par l’AMP; protéine p85α; voie de signalisation de l’insuline