Swimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM

Zhe Zhang,1,2 Di Cui,1,2 Tan Zhang,1,2 Yi Sun,1,2 Shuzhe Ding1,2 1Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, People’s Republic of China; 2College of Physical Education and Health, East Ch...

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Autores principales:	Zhang Z, Cui D, Zhang T, Sun Y, Ding S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	t2dm skeletal muscle mitochondrial quality ers mam Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/7978b088f0914be49f95b79ff2717751
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spelling	oai:doaj.org-article:7978b088f0914be49f95b79ff27177512021-12-02T08:36:38ZSwimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM1178-7007https://doaj.org/article/7978b088f0914be49f95b79ff27177512020-04-01T00:00:00Zhttps://www.dovepress.com/swimming-differentially-affects-t2dm-induced-skeletal-muscle-er-stress-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Zhe Zhang,1,2 Di Cui,1,2 Tan Zhang,1,2 Yi Sun,1,2 Shuzhe Ding1,2 1Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, People’s Republic of China; 2College of Physical Education and Health, East China Normal University, Shanghai 200241, People’s Republic of ChinaCorrespondence: Shuzhe DingKey Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, People’s Republic of ChinaTel +86 13601798505Email szding@tyxx.ecnu.edu.cnPurpose: Mitochondrial dysfunction and endoplasmic reticulum stress (ERS) are associated with metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). Mitochondria and ER are connected via mitochondria-associated membranes (MAM) that are involved in glucose homeostasis and insulin resistance. We postulated that exercise might positively benefit T2DM-induced ER and mitochondrial dysfunction that might be associated with MAM.Materials and Methods: Mice were fed a high-fat diet and injected with streptozotocin (STZ) to create T2DM models. Glucose tolerance, mitochondrial quality, MAM quality, and ERS were investigated in diabetic mice after six weeks of swimming.Results: Type 2 DM induced decreased MAM quantity, impaired mitochondrial quality, and deteriorated ERS in skeletal muscle that led to endoplasmic reticulum-associated degradation (ERAD). Swimming alleviated strong ERS caused by T2DM. Importantly, MAM quantity was positively associated with mitochondrial function and tended to negatively correlate with the ERS branch, ATF6. Moreover, both ATF6 branches of ERS and ERAD were positively associated with the pIRE1α branch of ERS.Conclusion: Type 2 DM induced glucose intolerance, powerful ERS, and mitochondrial dysfunction associated with decreased amounts of MAM. Swimming improved glucose intolerance and selectively mitigated the ERS in skeletal muscle. Therefore, MAM quality and ATF6 might be novel and important targets for T2DM treatment. Endoplasmic reticulum stress might be an effective target of swimming to improve diabetes.Keywords: T2DM, skeletal muscle, mitochondrial quality, ERS, MAMZhang ZCui DZhang TSun YDing SDove Medical Pressarticlet2dmskeletal musclemitochondrial qualityersmamSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 1417-1428 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	t2dm skeletal muscle mitochondrial quality ers mam Specialties of internal medicine RC581-951
spellingShingle	t2dm skeletal muscle mitochondrial quality ers mam Specialties of internal medicine RC581-951 Zhang Z Cui D Zhang T Sun Y Ding S Swimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM
description	Zhe Zhang,1,2 Di Cui,1,2 Tan Zhang,1,2 Yi Sun,1,2 Shuzhe Ding1,2 1Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, People’s Republic of China; 2College of Physical Education and Health, East China Normal University, Shanghai 200241, People’s Republic of ChinaCorrespondence: Shuzhe DingKey Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, People’s Republic of ChinaTel +86 13601798505Email szding@tyxx.ecnu.edu.cnPurpose: Mitochondrial dysfunction and endoplasmic reticulum stress (ERS) are associated with metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). Mitochondria and ER are connected via mitochondria-associated membranes (MAM) that are involved in glucose homeostasis and insulin resistance. We postulated that exercise might positively benefit T2DM-induced ER and mitochondrial dysfunction that might be associated with MAM.Materials and Methods: Mice were fed a high-fat diet and injected with streptozotocin (STZ) to create T2DM models. Glucose tolerance, mitochondrial quality, MAM quality, and ERS were investigated in diabetic mice after six weeks of swimming.Results: Type 2 DM induced decreased MAM quantity, impaired mitochondrial quality, and deteriorated ERS in skeletal muscle that led to endoplasmic reticulum-associated degradation (ERAD). Swimming alleviated strong ERS caused by T2DM. Importantly, MAM quantity was positively associated with mitochondrial function and tended to negatively correlate with the ERS branch, ATF6. Moreover, both ATF6 branches of ERS and ERAD were positively associated with the pIRE1α branch of ERS.Conclusion: Type 2 DM induced glucose intolerance, powerful ERS, and mitochondrial dysfunction associated with decreased amounts of MAM. Swimming improved glucose intolerance and selectively mitigated the ERS in skeletal muscle. Therefore, MAM quality and ATF6 might be novel and important targets for T2DM treatment. Endoplasmic reticulum stress might be an effective target of swimming to improve diabetes.Keywords: T2DM, skeletal muscle, mitochondrial quality, ERS, MAM
format	article
author	Zhang Z Cui D Zhang T Sun Y Ding S
author_facet	Zhang Z Cui D Zhang T Sun Y Ding S
author_sort	Zhang Z
title	Swimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM
title_short	Swimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM
title_full	Swimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM
title_fullStr	Swimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM
title_full_unstemmed	Swimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM
title_sort	swimming differentially affects t2dm-induced skeletal muscle er stress and mitochondrial dysfunction related to mam
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/7978b088f0914be49f95b79ff2717751
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Swimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM

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