Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells

Latha Ramalingam, Boontharick Sopontammarak, Kalhara R Menikdiwela, Naima Moustaid-Moussa Department of Nutritional Sciences, And Obesity Research Institute, Texas Tech University, Lubbock, TX 79424, USACorrespondence: Naima Moustaid-MoussaTexas Tech University, Department of Nutritional Sciences &a...

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Autores principales:	Ramalingam L, Sopontammarak B, Menikdiwela KR, Moustaid-Moussa N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	beta cells renin angiotensin aldosterone system (raas) type 2 diabetes er stress inflammation Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/2aed9d6cc7d14f4e9ebcb91855f0a599
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spelling	oai:doaj.org-article:2aed9d6cc7d14f4e9ebcb91855f0a5992021-12-02T11:25:03ZEndoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells1178-7007https://doaj.org/article/2aed9d6cc7d14f4e9ebcb91855f0a5992020-08-01T00:00:00Zhttps://www.dovepress.com/endoplasmic-reticulum-er-stress-in-part-mediates-effects-of-angiotensi-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Latha Ramalingam, Boontharick Sopontammarak, Kalhara R Menikdiwela, Naima Moustaid-Moussa Department of Nutritional Sciences, And Obesity Research Institute, Texas Tech University, Lubbock, TX 79424, USACorrespondence: Naima Moustaid-MoussaTexas Tech University, Department of Nutritional Sciences & Obesity Research Institute, 1301 Akron Street, Lubbock, TX 79409-1270, USATel + 806-834-7946Email naima.moustaid-moussa@ttu.eduIntroduction: The renin angiotensin aldosterone system (RAAS) is a hormone system known for its role in regulating blood pressure and fluid balance. Numerous RAAS inhibitors routinely prescribed for hypertension have also beneficial effects in type 2 diabetes (T2D) prevention. RAAS components are expressed locally in many tissues, including adipose tissue and pancreas, where they exert metabolic effects through RAAS bioactive hormone angiotensin II (Ang II). Pancreatic beta cells are specialized insulin-producing cells; they have also developed endoplasmic reticulum (ER), which contributes to beta cell dysfunction, when proteins are misfolded in disease states such as T2D. However, no studies have investigated the relationship between RAAS and ER stress in beta cells as a mechanism linking pancreatic RAAS to T2D. Hence, we hypothesized that Ang II treatment of beta cells increases ER stress and inflammation leading to reduced insulin secretion.Methods: To test this hypothesis, we treated clonal INS-1E beta cells and human islets with Ang II and assessed changes in ER stress markers. INS-1E beta cells were also used for measuring insulin secretion and for assessing the effects of various RAAS and ER stress inhibitors.Results: We demonstrated that Ang II significantly increased the expression of ER stress genes such as Chop and Atf4 and reduced insulin secretion. Furthermore, inhibition of Ang II production with an angiotensin converting enzyme inhibitor (ACEi, captopril) significantly reduced ER stress. Moreover, the Ang II receptor blockade reduced ER stress significantly and rescued insulin secretion.Discussion: This research provides new mechanistic insight into the role of RAAS activation via ER stress on beta cell dysfunction and provides additional evidence for protective effects of RAAS inhibition in T2D.Keywords: beta cells, renin angiotensin aldosterone system, RAAS, type 2 diabetes, ER stress, inflammationRamalingam LSopontammarak BMenikdiwela KRMoustaid-Moussa NDove Medical Pressarticlebeta cellsrenin angiotensin aldosterone system (raas)type 2 diabeteser stressinflammationSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 2843-2853 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	beta cells renin angiotensin aldosterone system (raas) type 2 diabetes er stress inflammation Specialties of internal medicine RC581-951
spellingShingle	beta cells renin angiotensin aldosterone system (raas) type 2 diabetes er stress inflammation Specialties of internal medicine RC581-951 Ramalingam L Sopontammarak B Menikdiwela KR Moustaid-Moussa N Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells
description	Latha Ramalingam, Boontharick Sopontammarak, Kalhara R Menikdiwela, Naima Moustaid-Moussa Department of Nutritional Sciences, And Obesity Research Institute, Texas Tech University, Lubbock, TX 79424, USACorrespondence: Naima Moustaid-MoussaTexas Tech University, Department of Nutritional Sciences & Obesity Research Institute, 1301 Akron Street, Lubbock, TX 79409-1270, USATel + 806-834-7946Email naima.moustaid-moussa@ttu.eduIntroduction: The renin angiotensin aldosterone system (RAAS) is a hormone system known for its role in regulating blood pressure and fluid balance. Numerous RAAS inhibitors routinely prescribed for hypertension have also beneficial effects in type 2 diabetes (T2D) prevention. RAAS components are expressed locally in many tissues, including adipose tissue and pancreas, where they exert metabolic effects through RAAS bioactive hormone angiotensin II (Ang II). Pancreatic beta cells are specialized insulin-producing cells; they have also developed endoplasmic reticulum (ER), which contributes to beta cell dysfunction, when proteins are misfolded in disease states such as T2D. However, no studies have investigated the relationship between RAAS and ER stress in beta cells as a mechanism linking pancreatic RAAS to T2D. Hence, we hypothesized that Ang II treatment of beta cells increases ER stress and inflammation leading to reduced insulin secretion.Methods: To test this hypothesis, we treated clonal INS-1E beta cells and human islets with Ang II and assessed changes in ER stress markers. INS-1E beta cells were also used for measuring insulin secretion and for assessing the effects of various RAAS and ER stress inhibitors.Results: We demonstrated that Ang II significantly increased the expression of ER stress genes such as Chop and Atf4 and reduced insulin secretion. Furthermore, inhibition of Ang II production with an angiotensin converting enzyme inhibitor (ACEi, captopril) significantly reduced ER stress. Moreover, the Ang II receptor blockade reduced ER stress significantly and rescued insulin secretion.Discussion: This research provides new mechanistic insight into the role of RAAS activation via ER stress on beta cell dysfunction and provides additional evidence for protective effects of RAAS inhibition in T2D.Keywords: beta cells, renin angiotensin aldosterone system, RAAS, type 2 diabetes, ER stress, inflammation
format	article
author	Ramalingam L Sopontammarak B Menikdiwela KR Moustaid-Moussa N
author_facet	Ramalingam L Sopontammarak B Menikdiwela KR Moustaid-Moussa N
author_sort	Ramalingam L
title	Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells
title_short	Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells
title_full	Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells
title_fullStr	Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells
title_full_unstemmed	Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells
title_sort	endoplasmic reticulum (er) stress in part mediates effects of angiotensin ii in pancreatic beta cells
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/2aed9d6cc7d14f4e9ebcb91855f0a599
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_version_	1718395929107628032

Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells

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