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Loss of ACE2 Exaggerates High-Calorie Diet–Induced Insulin Resistance by Reduction of GLUT4 in Mice
ACE type 2 (ACE2) functions as a negative regulator of the renin-angiotensin system by cleaving angiotensin II (AII) into angiotensin 1–7 (A1–7). This study assessed the role of endogenous ACE2 in maintaining insulin sensitivity. Twelve-week-old male ACE2 knockout (ACE2KO) mice had normal insulin se...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526031/ https://www.ncbi.nlm.nih.gov/pubmed/22933108 http://dx.doi.org/10.2337/db12-0177 |
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author | Takeda, Masao Yamamoto, Koichi Takemura, Yukihiro Takeshita, Hikari Hongyo, Kazuhiro Kawai, Tatsuo Hanasaki-Yamamoto, Hiroko Oguro, Ryosuke Takami, Yoichi Tatara, Yuji Takeya, Yasushi Sugimoto, Ken Kamide, Kei Ohishi, Mitsuru Rakugi, Hiromi |
author_facet | Takeda, Masao Yamamoto, Koichi Takemura, Yukihiro Takeshita, Hikari Hongyo, Kazuhiro Kawai, Tatsuo Hanasaki-Yamamoto, Hiroko Oguro, Ryosuke Takami, Yoichi Tatara, Yuji Takeya, Yasushi Sugimoto, Ken Kamide, Kei Ohishi, Mitsuru Rakugi, Hiromi |
author_sort | Takeda, Masao |
collection | PubMed |
description | ACE type 2 (ACE2) functions as a negative regulator of the renin-angiotensin system by cleaving angiotensin II (AII) into angiotensin 1–7 (A1–7). This study assessed the role of endogenous ACE2 in maintaining insulin sensitivity. Twelve-week-old male ACE2 knockout (ACE2KO) mice had normal insulin sensitivities when fed a standard diet. AII infusion or a high-fat, high-sucrose (HFHS) diet impaired glucose tolerance and insulin sensitivity more severely in ACE2KO mice than in their wild-type (WT) littermates. The strain difference in glucose tolerance was not eliminated by an AII receptor type 1 (AT1) blocker but was eradicated by A1–7 or an AT1 blocker combined with the A1–7 inhibitor (A779). The expression of GLUT4 and a transcriptional factor, myocyte enhancer factor (MEF) 2A, was dramatically reduced in the skeletal muscles of the standard diet–fed ACE2KO mice. The expression of GLUT4 and MEF2A was increased by A1–7 in ACE2KO mice and decreased by A779 in WT mice. A1–7 enhanced upregulation of MEF2A and GLUT4 during differentiation of myoblast cells. In conclusion, ACE2 protects against high-calorie diet–induced insulin resistance in mice. This mechanism may involve the transcriptional regulation of GLUT4 via an A1–7–dependent pathway. |
format | Online Article Text |
id | pubmed-3526031 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-35260312014-01-01 Loss of ACE2 Exaggerates High-Calorie Diet–Induced Insulin Resistance by Reduction of GLUT4 in Mice Takeda, Masao Yamamoto, Koichi Takemura, Yukihiro Takeshita, Hikari Hongyo, Kazuhiro Kawai, Tatsuo Hanasaki-Yamamoto, Hiroko Oguro, Ryosuke Takami, Yoichi Tatara, Yuji Takeya, Yasushi Sugimoto, Ken Kamide, Kei Ohishi, Mitsuru Rakugi, Hiromi Diabetes Pathophysiology ACE type 2 (ACE2) functions as a negative regulator of the renin-angiotensin system by cleaving angiotensin II (AII) into angiotensin 1–7 (A1–7). This study assessed the role of endogenous ACE2 in maintaining insulin sensitivity. Twelve-week-old male ACE2 knockout (ACE2KO) mice had normal insulin sensitivities when fed a standard diet. AII infusion or a high-fat, high-sucrose (HFHS) diet impaired glucose tolerance and insulin sensitivity more severely in ACE2KO mice than in their wild-type (WT) littermates. The strain difference in glucose tolerance was not eliminated by an AII receptor type 1 (AT1) blocker but was eradicated by A1–7 or an AT1 blocker combined with the A1–7 inhibitor (A779). The expression of GLUT4 and a transcriptional factor, myocyte enhancer factor (MEF) 2A, was dramatically reduced in the skeletal muscles of the standard diet–fed ACE2KO mice. The expression of GLUT4 and MEF2A was increased by A1–7 in ACE2KO mice and decreased by A779 in WT mice. A1–7 enhanced upregulation of MEF2A and GLUT4 during differentiation of myoblast cells. In conclusion, ACE2 protects against high-calorie diet–induced insulin resistance in mice. This mechanism may involve the transcriptional regulation of GLUT4 via an A1–7–dependent pathway. American Diabetes Association 2013-01 2012-12-13 /pmc/articles/PMC3526031/ /pubmed/22933108 http://dx.doi.org/10.2337/db12-0177 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Pathophysiology Takeda, Masao Yamamoto, Koichi Takemura, Yukihiro Takeshita, Hikari Hongyo, Kazuhiro Kawai, Tatsuo Hanasaki-Yamamoto, Hiroko Oguro, Ryosuke Takami, Yoichi Tatara, Yuji Takeya, Yasushi Sugimoto, Ken Kamide, Kei Ohishi, Mitsuru Rakugi, Hiromi Loss of ACE2 Exaggerates High-Calorie Diet–Induced Insulin Resistance by Reduction of GLUT4 in Mice |
title | Loss of ACE2 Exaggerates High-Calorie Diet–Induced Insulin Resistance by Reduction of GLUT4 in Mice |
title_full | Loss of ACE2 Exaggerates High-Calorie Diet–Induced Insulin Resistance by Reduction of GLUT4 in Mice |
title_fullStr | Loss of ACE2 Exaggerates High-Calorie Diet–Induced Insulin Resistance by Reduction of GLUT4 in Mice |
title_full_unstemmed | Loss of ACE2 Exaggerates High-Calorie Diet–Induced Insulin Resistance by Reduction of GLUT4 in Mice |
title_short | Loss of ACE2 Exaggerates High-Calorie Diet–Induced Insulin Resistance by Reduction of GLUT4 in Mice |
title_sort | loss of ace2 exaggerates high-calorie diet–induced insulin resistance by reduction of glut4 in mice |
topic | Pathophysiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526031/ https://www.ncbi.nlm.nih.gov/pubmed/22933108 http://dx.doi.org/10.2337/db12-0177 |
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