IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1?/?Mice Mediated by miR-33

Chen-Yi Tang; Xiao-Fei Man; Yue Guo; Hao-Neng Tang; Jun Tang; Ci-La Zhou; Shu-Wen Tan; Min Wang; Hou-De Zhou

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자료유형: 학술저널

저자정보: Chen-Yi Tang (Central South University) Xiao-Fei Man (Central South University) Yue Guo (Central South University) Hao-Neng Tang (Central South University) Jun Tang (Central South University) Ci-La Zhou (Central South University) Shu-Wen Tan (Central South University) Min Wang (Central South University) Hou-De Zhou (Central South University)

저널정보: 한국분자세포생물학회 Molecules and Cells Molecules and Cells 제40권 제2호

발행연도: 2017.2

수록면: 123 - 132 (10page)

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Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse (Irs-1?/?) with growth retardation and subcutaneous adipocyte atrophy. Irs-1?/? mice exhibited mild insulin resistance, as demonstrat-ed by the insulin tolerance test. Phosphatidylino-sitol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcu-taneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of Irs-1?/? mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What’s more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of Irs-1?/? mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

#insulin signaling pathway #IRS-1 #IRS-2 #miR-33

참고문헌 (44)

참고문헌 신청

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