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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
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.
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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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