GABAergic system in the endocrine pancreas: a new target for diabetes treatment

Yun Wan,1 Qinghua Wang,1–3 Gerald J Prud’homme4,5 1Department of Endocrinology and Metabolism, Huashan Hospital, Medical College, Fudan University, Shanghai, People’s Republic of China; 2Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Sc...

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Autores principales:	Wan Y, Wang Q, Prud’homme GJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/4774e9c51e6f42f792c35670dd15e233
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spelling	oai:doaj.org-article:4774e9c51e6f42f792c35670dd15e2332021-12-02T00:34:45ZGABAergic system in the endocrine pancreas: a new target for diabetes treatment1178-7007https://doaj.org/article/4774e9c51e6f42f792c35670dd15e2332015-02-01T00:00:00Zhttp://www.dovepress.com/gabaergic-system-in-the-endocrine-pancreas-a-new-target-for-diabetes-t-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007 Yun Wan,1 Qinghua Wang,1–3 Gerald J Prud’homme4,5 1Department of Endocrinology and Metabolism, Huashan Hospital, Medical College, Fudan University, Shanghai, People’s Republic of China; 2Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science of St Michael’s Hospital, 3Departments of Physiology and Medicine, Faculty of Medicine, 4Department of Laboratory Medicine and Pathobiology, University of Toronto, 5Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St Michael’s Hospital, Toronto, ON, Canada Abstract: Excessive loss of functional pancreatic β-cell mass, mainly due to apoptosis, is a major factor in the development of hyperglycemia in both type 1 and type 2 diabetes (T1D and T2D). In T1D, β-cells are destroyed by immunological mechanisms. In T2D, while metabolic factors are known to contribute to β-cell failure and subsequent apoptosis, mounting evidence suggests that islet inflammation also plays an important role in the loss of β-cell mass. Therefore, it is of great importance for clinical intervention to develop new therapies. γ-Aminobutyric acid (GABA), a major neurotransmitter, is also produced by islet β-cells, where it functions as an important intraislet transmitter in regulating islet-cell secretion and function. Importantly, recent studies performed in rodents, including in vivo studies of xenotransplanted human islets, reveal that GABA exerts β-cell regenerative effects. Moreover, it protects β-cells against apoptosis induced by cytokines, drugs, and other stresses, and has anti-inflammatory and immunoregulatory activities. It ameliorates the manifestations of diabetes in preclinical models, suggesting potential applications for the treatment of diabetic patients. This review outlines the actions of GABA relevant to β-cell regeneration, including its signaling mechanisms and potential interactions with other mediators. These studies increase our understanding of the regenerative processes of pancreatic β-cells, and help pave the way for the development of regenerative medicine for diabetes. Keywords: β-cell, proliferation, apoptosis, GABA, ion channel, insulin, glucagon, inflammation, diabetesWan YWang QPrud’homme GJDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2015, Iss default, Pp 79-87 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Wan Y Wang Q Prud’homme GJ GABAergic system in the endocrine pancreas: a new target for diabetes treatment
description	Yun Wan,1 Qinghua Wang,1–3 Gerald J Prud’homme4,5 1Department of Endocrinology and Metabolism, Huashan Hospital, Medical College, Fudan University, Shanghai, People’s Republic of China; 2Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science of St Michael’s Hospital, 3Departments of Physiology and Medicine, Faculty of Medicine, 4Department of Laboratory Medicine and Pathobiology, University of Toronto, 5Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St Michael’s Hospital, Toronto, ON, Canada Abstract: Excessive loss of functional pancreatic β-cell mass, mainly due to apoptosis, is a major factor in the development of hyperglycemia in both type 1 and type 2 diabetes (T1D and T2D). In T1D, β-cells are destroyed by immunological mechanisms. In T2D, while metabolic factors are known to contribute to β-cell failure and subsequent apoptosis, mounting evidence suggests that islet inflammation also plays an important role in the loss of β-cell mass. Therefore, it is of great importance for clinical intervention to develop new therapies. γ-Aminobutyric acid (GABA), a major neurotransmitter, is also produced by islet β-cells, where it functions as an important intraislet transmitter in regulating islet-cell secretion and function. Importantly, recent studies performed in rodents, including in vivo studies of xenotransplanted human islets, reveal that GABA exerts β-cell regenerative effects. Moreover, it protects β-cells against apoptosis induced by cytokines, drugs, and other stresses, and has anti-inflammatory and immunoregulatory activities. It ameliorates the manifestations of diabetes in preclinical models, suggesting potential applications for the treatment of diabetic patients. This review outlines the actions of GABA relevant to β-cell regeneration, including its signaling mechanisms and potential interactions with other mediators. These studies increase our understanding of the regenerative processes of pancreatic β-cells, and help pave the way for the development of regenerative medicine for diabetes. Keywords: β-cell, proliferation, apoptosis, GABA, ion channel, insulin, glucagon, inflammation, diabetes
format	article
author	Wan Y Wang Q Prud’homme GJ
author_facet	Wan Y Wang Q Prud’homme GJ
author_sort	Wan Y
title	GABAergic system in the endocrine pancreas: a new target for diabetes treatment
title_short	GABAergic system in the endocrine pancreas: a new target for diabetes treatment
title_full	GABAergic system in the endocrine pancreas: a new target for diabetes treatment
title_fullStr	GABAergic system in the endocrine pancreas: a new target for diabetes treatment
title_full_unstemmed	GABAergic system in the endocrine pancreas: a new target for diabetes treatment
title_sort	gabaergic system in the endocrine pancreas: a new target for diabetes treatment
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/4774e9c51e6f42f792c35670dd15e233
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GABAergic system in the endocrine pancreas: a new target for diabetes treatment

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