| Glucose promotion of GABA metabolism contributes to the stimulation of insulin secretion in β-cells. | |
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MedLine Citation:
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PMID: 20695849 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have demonstrated recently that branched-chain α-keto acid stimulation of insulin secretion is dependent on islet GABA (γ-aminobutyric acid) metabolism: GABA transamination to succinic semialdehyde is increased by 2-oxoglutarate, generated in α-keto acid transamination to its corresponding α-amino acid. The present work was aimed at investigating whether glucose also promotes islet GABA metabolism and whether the latter contributes to the stimulation of insulin secretion. Glucose (20 mM) decreased both the content and release of islet GABA. Gabaculine (1 mM), a GABA transaminase inhibitor, partially suppressed the secretory response of rat perifused islets to 20 mM glucose at different L-glutamine concentrations (0, 1 and 10 mM), as well as the glucose-induced decrease in islet GABA. The drug also reduced islet ATP content and the ATP/ADP ratio at 20 mM glucose. Exogenous succinic semialdehyde induced a dose-dependent increase in islet GABA content by reversal of GABA transamination and a biphasic insulin secretion in the absence of glucose. It depolarized isolated β-cells and triggered action potential firing, accompanied by a reduction of membrane currents through ATP-sensitive K(+) channels. The gene expression and enzyme activity of GABA transaminase were severalfold higher than that of 2-oxoglutarate dehydrogenase in islet homogenates. We conclude that, at high glucose concentrations, there is an increased diversion of glucose metabolism from the citric acid cycle into the 'GABA shunt'. Semialdehyde succinic acid is a cell-permeant 'GABA-shunt' metabolite that increases ATP and the ATP/ADP ratio, depolarizes β-cells and stimulates insulin secretion. In summary, an increased islet GABA metabolism may trigger insulin secretion. |
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Authors:
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Javier Pizarro-Delgado; Matthias Braun; Inés Hernández-Fisac; Rafael Martín-Del-Río; Jorge Tamarit-Rodriguez |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 431 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-12 Completed Date: 2010-10-27 Revised Date: 2011-09-06 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 381-9 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Complutense University, Madrid, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Glucose / metabolism* Insulin / secretion* Insulin-Secreting Cells / metabolism*, secretion* Male Membrane Potentials Patch-Clamp Techniques Rats Rats, Wistar gamma-Aminobutyric Acid / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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//Medical Research Council; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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11061-68-0/Insulin; 50-99-7/Glucose; 56-12-2/gamma-Aminobutyric Acid; 56-65-5/Adenosine Triphosphate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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