Document Detail

Glucagon-like peptide-1 stimulates GABA formation by pancreatic beta-cells at the level of glutamate decarboxylase.
MedLine Citation:
PMID:  17190904     Owner:  NLM     Status:  MEDLINE    
Pancreatic beta-cells are the major extraneural site of glutamate decarboxylase expression (GAD). During culture of isolated beta-cells, the GAD product gamma-aminobutyrate (GABA) is rapidly released in the medium, independently of insulin. It is considered as a possible mediator of beta-cell influences on alpha-cells, acinar cells, and/or infiltrating lymphocytes. In this perspective, we investigated the regulation of GABA release by rat beta-cells during a 24-h culture period. Glucose was previously reported to inhibit GABA release by diverting cellular GABA to mitochondrial breakdown through activation of GABA transferase (GABA-T). In the present study, glucagon-like peptide-1 (GLP-1) was shown to stimulate GABA formation at the level of GAD, its effect being suppressed by the GAD inhibitor allylglycine and remaining unaltered by the GABA-T inhibitor gamma-vinyl-GABA. The stimulatory action of GLP-1 is cAMP dependent, being reproduced by the adenylate cyclase activator forskolin and the cAMP analog N(6)-benzoyladenosine-3',5'-cAMP and inhibited by a PKA inhibitor. It is dependent on protein synthesis and associated with an increased expression of GAD67 but not GAD65. The GLP-1-induced stimulation of GAD activity in beta-cells can elevate medium GABA levels in conditions of glucose-driven intracellular GABA breakdown and thus maintain GABA-mediated beta-cell influences on neighboring cells.
Chen Wang; Rui Mao; Mark Van de Casteele; Daniel Pipeleers; Zhidong Ling
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-12-26
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  292     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-02     Completed Date:  2007-05-21     Revised Date:  2007-10-24    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1201-6     Citation Subset:  IM    
Diabetes Research Center, Brussels Free University-VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium.
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MeSH Terms
Adenylate Cyclase / metabolism
Calcium / metabolism
Cells, Cultured
Cyclic AMP / analogs & derivatives,  metabolism
Enzyme Activation / drug effects
Forskolin / pharmacology
Glucagon-Like Peptide 1 / antagonists & inhibitors,  pharmacology*
Glutamate Decarboxylase / metabolism*
Insulin-Secreting Cells / enzymology,  metabolism*
Isoenzymes / metabolism
Rats, Wistar
gamma-Aminobutyric Acid / biosynthesis*
Reg. No./Substance:
0/Isoenzymes; 56-12-2/gamma-Aminobutyric Acid; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 7440-70-2/Calcium; 89750-14-1/Glucagon-Like Peptide 1; EC Decarboxylase; EC decarboxylase 1; EC Cyclase

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