| Oxo-4-methylpentanoic acid directs the metabolism of GABA into the Krebs cycle in rat pancreatic islets. | |
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MedLine Citation:
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PMID: 16819942 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OMP (oxo-4-methylpentanoic acid) stimulates by itself a biphasic secretion of insulin whereas L-leucine requires the presence of L-glutamine. L-Glutamine is predominantly converted into GABA (gamma-aminobutyric acid) in rat islets and L-leucine seems to promote its metabolism in the 'GABA shunt' [Fernández-Pascual, Mukala-Nsengu-Tshibangu, Martín del Río and Tamarit-Rodríguez (2004) Biochem. J. 379, 721-729]. In the present study, we have investigated how 10 mM OMP affects L-glutamine metabolism to uncover possible differences with L-leucine that might help to elucidate whether they share a common mechanism of stimulation of insulin secretion. In contrast with L-leucine, OMP alone stimulated a biphasic insulin secretion in rat perifused islets and decreased the islet content of GABA without modifying its extracellular release irrespective of the concentration of L-glutamine in the medium. GABA was transaminated to L-leucine whose intracellular concentration did not change because it was efficiently transported out of the islet cells. The L-[U-14C]-Glutamine (at 0.5 and 10.0 mM) conversion to 14CO2 was enhanced by 10 mM OMP within 30% and 70% respectively. Gabaculine (250 microM), a GABA transaminase inhibitor, suppressed OMP-induced oxygen consumption but not L-leucine- or glucose-stimulated respiration. It also suppressed the OMP-induced decrease in islet GABA content and the OMP-induced increase in insulin release. These results support the view that OMP promotes islet metabolism in the 'GABA shunt' generating 2-oxo-glutarate, in the branched-chain alpha-amino acid transaminase reaction, which would in turn trigger GABA deamination by GABA transaminase. OMP, but not L-leucine, suppressed islet semialdehyde succinic acid reductase activity and this might shift the metabolic flux of the 'GABA shunt' from gamma-hydroxybutyrate to succinic acid production. |
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Authors:
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Inés Hernández-Fisac; Sergio Fernández-Pascual; Henrik Ortsäter; Javier Pizarro-Delgado; Rafael Martín del Río; Peter Bergsten; Jorge Tamarit-Rodriguez |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 400 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2006 Nov |
Date Detail:
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Created Date: 2006-10-25 Completed Date: 2006-11-27 Revised Date: 2009-11-18 |
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: 81-9 Citation Subset: IM |
Affiliation:
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Biochemistry Department, Medical School, Complutense University, Madrid-28040, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldehyde Oxidoreductases
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antagonists & inhibitors,
metabolism Amino Acids / metabolism Animals Cerebellum / drug effects, enzymology, metabolism Citric Acid Cycle / drug effects* Cyclohexanecarboxylic Acids / pharmacology Glucose / pharmacology Glutamine / metabolism, pharmacology Insulin / secretion Islets of Langerhans / drug effects*, metabolism Keto Acids / pharmacology* Leucine / pharmacology Male Oxidation-Reduction / drug effects Oxygen / metabolism Rats Rats, Wistar Succinate-Semialdehyde Dehydrogenase / antagonists & inhibitors, metabolism Time Factors Transaminases / antagonists & inhibitors, metabolism gamma-Aminobutyric Acid / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Cyclohexanecarboxylic Acids; 0/Keto Acids; 11061-68-0/Insulin; 50-99-7/Glucose; 56-12-2/gamma-Aminobutyric Acid; 56-85-9/Glutamine; 61-90-5/Leucine; 7782-44-7/Oxygen; 816-66-0/alpha-ketoisocaproic acid; 87980-11-8/gabaculine; EC 1.2.-/Aldehyde Oxidoreductases; EC 1.2.1.24/Succinate-Semialdehyde Dehydrogenase; EC 2.6.1.-/Transaminases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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