Cargando…

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

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 i...

Descripción completa

Detalles Bibliográficos
Autores principales: Tang, Chen-Yi, Man, Xiao-Fei, Guo, Yue, Tang, Hao-Neng, Tang, Jun, Zhou, Ci-La, Tan, Shu-Wen, Wang, Min, Zhou, Hou-De
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339503/
https://www.ncbi.nlm.nih.gov/pubmed/28190325
http://dx.doi.org/10.14348/molcells.2017.2228
_version_ 1782512670068441088
author Tang, Chen-Yi
Man, Xiao-Fei
Guo, Yue
Tang, Hao-Neng
Tang, Jun
Zhou, Ci-La
Tan, Shu-Wen
Wang, Min
Zhou, Hou-De
author_facet Tang, Chen-Yi
Man, Xiao-Fei
Guo, Yue
Tang, Hao-Neng
Tang, Jun
Zhou, Ci-La
Tan, Shu-Wen
Wang, Min
Zhou, Hou-De
author_sort Tang, Chen-Yi
collection PubMed
description 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 demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous 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.
format Online
Article
Text
id pubmed-5339503
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Korean Society for Molecular and Cellular Biology
record_format MEDLINE/PubMed
spelling pubmed-53395032017-03-28 IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1(−/−) Mice Mediated by miR-33 Tang, Chen-Yi Man, Xiao-Fei Guo, Yue Tang, Hao-Neng Tang, Jun Zhou, Ci-La Tan, Shu-Wen Wang, Min Zhou, Hou-De Mol Cells Article 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 demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous 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. Korean Society for Molecular and Cellular Biology 2017-02-28 2017-02-13 /pmc/articles/PMC5339503/ /pubmed/28190325 http://dx.doi.org/10.14348/molcells.2017.2228 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.
spellingShingle Article
Tang, Chen-Yi
Man, Xiao-Fei
Guo, Yue
Tang, Hao-Neng
Tang, Jun
Zhou, Ci-La
Tan, Shu-Wen
Wang, Min
Zhou, Hou-De
IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1(−/−) Mice Mediated by miR-33
title IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1(−/−) Mice Mediated by miR-33
title_full IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1(−/−) Mice Mediated by miR-33
title_fullStr IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1(−/−) Mice Mediated by miR-33
title_full_unstemmed IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1(−/−) Mice Mediated by miR-33
title_short IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1(−/−) Mice Mediated by miR-33
title_sort irs-2 partially compensates for the insulin signal defects in irs-1(−/−) mice mediated by mir-33
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339503/
https://www.ncbi.nlm.nih.gov/pubmed/28190325
http://dx.doi.org/10.14348/molcells.2017.2228
work_keys_str_mv AT tangchenyi irs2partiallycompensatesfortheinsulinsignaldefectsinirs1micemediatedbymir33
AT manxiaofei irs2partiallycompensatesfortheinsulinsignaldefectsinirs1micemediatedbymir33
AT guoyue irs2partiallycompensatesfortheinsulinsignaldefectsinirs1micemediatedbymir33
AT tanghaoneng irs2partiallycompensatesfortheinsulinsignaldefectsinirs1micemediatedbymir33
AT tangjun irs2partiallycompensatesfortheinsulinsignaldefectsinirs1micemediatedbymir33
AT zhoucila irs2partiallycompensatesfortheinsulinsignaldefectsinirs1micemediatedbymir33
AT tanshuwen irs2partiallycompensatesfortheinsulinsignaldefectsinirs1micemediatedbymir33
AT wangmin irs2partiallycompensatesfortheinsulinsignaldefectsinirs1micemediatedbymir33
AT zhouhoude irs2partiallycompensatesfortheinsulinsignaldefectsinirs1micemediatedbymir33