| GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. | |
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MedLine Citation:
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PMID: 21709230 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Type 1 diabetes (T1D) is an autoimmune disease characterized by insulitis and islet β-cell loss. Thus, an effective therapy may require β-cell restoration and immune suppression. Currently, there is no treatment that can achieve both goals efficiently. We report here that GABA exerts antidiabetic effects by acting on both the islet β-cells and immune system. Unlike in adult brain or islet α-cells in which GABA exerts hyperpolarizing effects, in islet β-cells, GABA produces membrane depolarization and Ca(2+) influx, leading to the activation of PI3-K/Akt-dependent growth and survival pathways. This provides a potential mechanism underlying our in vivo findings that GABA therapy preserves β-cell mass and prevents the development of T1D. Remarkably, in severely diabetic mice, GABA restores β-cell mass and reverses the disease. Furthermore, GABA suppresses insulitis and systemic inflammatory cytokine production. The β-cell regenerative and immunoinhibitory effects of GABA provide insights into the role of GABA in regulating islet cell function and glucose homeostasis, which may find clinical application. |
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Authors:
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Nepton Soltani; Hongmin Qiu; Mila Aleksic; Yelena Glinka; Fang Zhao; Rui Liu; Yiming Li; Nina Zhang; Rabindranath Chakrabarti; Tiffany Ng; Tianru Jin; Haibo Zhang; Wei-Yang Lu; Zhong-Ping Feng; Gerald J Prud'homme; Qinghua Wang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-06-27 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-07-13 Completed Date: 2011-09-20 Revised Date: 2013-05-24 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 11692-7 Citation Subset: IM |
Affiliation:
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Division of Endocrinology and Metabolism, the Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada M5B 1W8. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects Calcium Signaling / drug effects Cell Proliferation / drug effects Cytokines / biosynthesis Diabetes Mellitus, Type 1 / drug therapy*, immunology, pathology, physiopathology Female Hyperglycemia / prevention & control Immunosuppressive Agents / pharmacology Inflammation Mediators / metabolism Insulin-Secreting Cells / drug effects*, immunology, pathology, physiology Male Membrane Potentials / drug effects Mice Mice, Inbred NOD Mice, Transgenic Phosphatidylinositol 3-Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism Regeneration / drug effects Signal Transduction / drug effects T-Lymphocytes, Regulatory / drug effects, immunology gamma-Aminobutyric Acid / pharmacology*, physiology |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Immunosuppressive Agents; 0/Inflammation Mediators; 56-12-2/gamma-Aminobutyric Acid; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
| Comments/Corrections | |
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