Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.

<h4>Background</h4>The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS) may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the...

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Autores principales:	Eliete Dalla Corte Frantz, Camila Crespo-Mascarenhas, Andre Rodrigues C Barreto-Vianna, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/155b6bcff49e435d88479510422226cd
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spelling	oai:doaj.org-article:155b6bcff49e435d88479510422226cd2021-11-18T09:03:42ZRenin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.1932-620310.1371/journal.pone.0067192https://doaj.org/article/155b6bcff49e435d88479510422226cd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894285/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS) may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the regulation of the pancreas and glucose intolerance of mice fed high-fat (HF) diet.<h4>Methods</h4>C57BL/6 mice fed a HF diet (8 weeks) were treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for 6 weeks, and the protective effects were extensively compared among groups by morphometry, stereological tools, immunostaining, Western blotting and hormonal analysis.<h4>Results</h4>All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated body mass (BM) gain, glucose intolerance and insulin resistance, improved the alpha and beta cell mass and prevented the reduction of plasma adiponectin. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression.<h4>Conclusion</h4>Our findings indicate that ACE inhibition with enalapril attenuated several of the deleterious effects of the HF diet. In summary, enalapril appears to be responsible for the normalization of islet morphology and function, of alpha and beta cell mass and of Pdx1 and GLUT2 expression. These protective effects of enalapril were attributed, primarily, to the reduction in body mass gain and food intake and the enhancement of the ACE2/Ang (1-7) /Mas receptor axis and adiponectin levels.Eliete Dalla Corte FrantzCamila Crespo-MascarenhasAndre Rodrigues C Barreto-ViannaMarcia Barbosa AguilaCarlos Alberto Mandarim-de-LacerdaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e67192 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eliete Dalla Corte Frantz Camila Crespo-Mascarenhas Andre Rodrigues C Barreto-Vianna Marcia Barbosa Aguila Carlos Alberto Mandarim-de-Lacerda Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.
description	<h4>Background</h4>The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS) may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the regulation of the pancreas and glucose intolerance of mice fed high-fat (HF) diet.<h4>Methods</h4>C57BL/6 mice fed a HF diet (8 weeks) were treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for 6 weeks, and the protective effects were extensively compared among groups by morphometry, stereological tools, immunostaining, Western blotting and hormonal analysis.<h4>Results</h4>All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated body mass (BM) gain, glucose intolerance and insulin resistance, improved the alpha and beta cell mass and prevented the reduction of plasma adiponectin. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression.<h4>Conclusion</h4>Our findings indicate that ACE inhibition with enalapril attenuated several of the deleterious effects of the HF diet. In summary, enalapril appears to be responsible for the normalization of islet morphology and function, of alpha and beta cell mass and of Pdx1 and GLUT2 expression. These protective effects of enalapril were attributed, primarily, to the reduction in body mass gain and food intake and the enhancement of the ACE2/Ang (1-7) /Mas receptor axis and adiponectin levels.
format	article
author	Eliete Dalla Corte Frantz Camila Crespo-Mascarenhas Andre Rodrigues C Barreto-Vianna Marcia Barbosa Aguila Carlos Alberto Mandarim-de-Lacerda
author_facet	Eliete Dalla Corte Frantz Camila Crespo-Mascarenhas Andre Rodrigues C Barreto-Vianna Marcia Barbosa Aguila Carlos Alberto Mandarim-de-Lacerda
author_sort	Eliete Dalla Corte Frantz
title	Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.
title_short	Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.
title_full	Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.
title_fullStr	Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.
title_full_unstemmed	Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.
title_sort	renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/155b6bcff49e435d88479510422226cd
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Renin-angiotensin system blockers protect pancreatic islets against diet-induced obesity and insulin resistance in mice.

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