Document Detail

GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes.
MedLine Citation:
PMID:  21709230     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-27
Journal Detail:
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:
Created Date:  2011-07-13     Completed Date:  2011-09-20     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11692-7     Citation Subset:  IM    
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:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Apoptosis / drug effects
Calcium Signaling / drug effects
Cell Proliferation / drug effects
Cytokines / biosynthesis
Diabetes Mellitus, Type 1 / drug therapy*,  immunology,  pathology,  physiopathology
Hyperglycemia / prevention & control
Immunosuppressive Agents / pharmacology
Inflammation Mediators / metabolism
Insulin-Secreting Cells / drug effects*,  immunology,  pathology,  physiology
Membrane Potentials / drug effects
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
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Cytokines; 0/Immunosuppressive Agents; 0/Inflammation Mediators; 56-12-2/gamma-Aminobutyric Acid; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Dehydro-alpha-lapachone, a plant product with antivascular activity.
Next Document:  Suppression of immune responses by nonimmunogenic oligodeoxynucleotides with high affinity for high-...