Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.

<h4>Objectives</h4>The role of angiotensin II type 2 (AT(2)) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT(2) receptor stimulation by compound 21 (C21) might contribute to possible insulin-sensitizing...

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Autores principales:	Kousei Ohshima, Masaki Mogi, Fei Jing, Jun Iwanami, Kana Tsukuda, Li-Juan Min, Akiyoshi Ogimoto, Björn Dahlöf, Ulrike M Steckelings, Tomas Unger, Jitsuo Higaki, Masatsugu Horiuchi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b1a49c707ed426aad42ef0986ee2c79
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spelling	oai:doaj.org-article:2b1a49c707ed426aad42ef0986ee2c792021-11-18T08:08:56ZDirect angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.1932-620310.1371/journal.pone.0048387https://doaj.org/article/2b1a49c707ed426aad42ef0986ee2c792012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23155382/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objectives</h4>The role of angiotensin II type 2 (AT(2)) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT(2) receptor stimulation by compound 21 (C21) might contribute to possible insulin-sensitizing/anti-diabetic effects in type 2 diabetes (T2DM) with PPARγ activation, mainly focusing on adipose tissue.<h4>Methods</h4>T2DM mice, KK-Ay, were subjected to intraperitoneal injection of C21 and/or a PPARγ antagonist, GW9662 in drinking water for 2 weeks. Insulin resistance was evaluated by oral glucose tolerance test, insulin tolerance test, and uptake of 2-[(3)H] deoxy-D-glucose in white adipose tissue. Morphological changes of adipose tissues as well as adipocyte differentiation and inflammatory response were examined.<h4>Results</h4>Treatment with C21 ameliorated insulin resistance in KK-Ay mice without influencing blood pressure, at least partially through effects on the PPARγ pathway. C21 treatment increased serum adiponectin concentration and decreased TNF-α concentration; however, these effects were attenuated by PPARγ blockade by co-treatment with GW9662. Moreover, we observed that administration of C21 enhanced adipocyte differentiation and PPARγ DNA-binding activity, with a decrease in inflammation in white adipose tissue, whereas these effects of C21 were attenuated by co-treatment with GW9662. We also observed that administration of C21 restored β cell damage in diabetic pancreatic tissue.<h4>Conclusion</h4>The present study demonstrated that direct AT(2) receptor stimulation by C21 accompanied with PPARγ activation ameliorated insulin resistance in T2DM mice, at least partially due to improvement of adipocyte dysfunction and protection of pancreatic β cells.Kousei OhshimaMasaki MogiFei JingJun IwanamiKana TsukudaLi-Juan MinAkiyoshi OgimotoBjörn DahlöfUlrike M SteckelingsTomas UngerJitsuo HigakiMasatsugu HoriuchiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e48387 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kousei Ohshima Masaki Mogi Fei Jing Jun Iwanami Kana Tsukuda Li-Juan Min Akiyoshi Ogimoto Björn Dahlöf Ulrike M Steckelings Tomas Unger Jitsuo Higaki Masatsugu Horiuchi Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.
description	<h4>Objectives</h4>The role of angiotensin II type 2 (AT(2)) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT(2) receptor stimulation by compound 21 (C21) might contribute to possible insulin-sensitizing/anti-diabetic effects in type 2 diabetes (T2DM) with PPARγ activation, mainly focusing on adipose tissue.<h4>Methods</h4>T2DM mice, KK-Ay, were subjected to intraperitoneal injection of C21 and/or a PPARγ antagonist, GW9662 in drinking water for 2 weeks. Insulin resistance was evaluated by oral glucose tolerance test, insulin tolerance test, and uptake of 2-[(3)H] deoxy-D-glucose in white adipose tissue. Morphological changes of adipose tissues as well as adipocyte differentiation and inflammatory response were examined.<h4>Results</h4>Treatment with C21 ameliorated insulin resistance in KK-Ay mice without influencing blood pressure, at least partially through effects on the PPARγ pathway. C21 treatment increased serum adiponectin concentration and decreased TNF-α concentration; however, these effects were attenuated by PPARγ blockade by co-treatment with GW9662. Moreover, we observed that administration of C21 enhanced adipocyte differentiation and PPARγ DNA-binding activity, with a decrease in inflammation in white adipose tissue, whereas these effects of C21 were attenuated by co-treatment with GW9662. We also observed that administration of C21 restored β cell damage in diabetic pancreatic tissue.<h4>Conclusion</h4>The present study demonstrated that direct AT(2) receptor stimulation by C21 accompanied with PPARγ activation ameliorated insulin resistance in T2DM mice, at least partially due to improvement of adipocyte dysfunction and protection of pancreatic β cells.
format	article
author	Kousei Ohshima Masaki Mogi Fei Jing Jun Iwanami Kana Tsukuda Li-Juan Min Akiyoshi Ogimoto Björn Dahlöf Ulrike M Steckelings Tomas Unger Jitsuo Higaki Masatsugu Horiuchi
author_facet	Kousei Ohshima Masaki Mogi Fei Jing Jun Iwanami Kana Tsukuda Li-Juan Min Akiyoshi Ogimoto Björn Dahlöf Ulrike M Steckelings Tomas Unger Jitsuo Higaki Masatsugu Horiuchi
author_sort	Kousei Ohshima
title	Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.
title_short	Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.
title_full	Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.
title_fullStr	Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.
title_full_unstemmed	Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.
title_sort	direct angiotensin ii type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with pparγ activation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2b1a49c707ed426aad42ef0986ee2c79
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Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.

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