RGD Reference Report - Mitochondrial GTP regulates glucose-stimulated insulin secretion. - Rat Genome Database

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Mitochondrial GTP regulates glucose-stimulated insulin secretion.

Authors: Kibbey, RG  Pongratz, RL  Romanelli, AJ  Wollheim, CB  Cline, GW  Shulman, GI 
Citation: Kibbey RG, etal., Cell Metab. 2007 Apr;5(4):253-64.
RGD ID: 2306915
Pubmed: PMID:17403370   (View Abstract at PubMed)
PMCID: PMC1876711   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cmet.2007.02.008   (Journal Full-text)

Nucleotide-specific isoforms of the tricarboxylic acid (TCA) cycle enzyme succinyl-CoA synthetase (SCS) catalyze substrate-level synthesis of mitochondrial GTP (mtGTP) and ATP (mtATP). While mtATP yield from glucose metabolism is coupled with oxidative phosphorylation and can vary, each molecule of glucose metabolized within pancreatic beta cells produces approximately one mtGTP, making mtGTP a potentially important fuel signal. In INS-1 832/13 cells and cultured rat islets, siRNA suppression of the GTP-producing pathway (DeltaSCS-GTP) reduced glucose-stimulated insulin secretion (GSIS) by 50%, while suppression of the ATP-producing isoform (DeltaSCS-ATP) increased GSIS 2-fold. Insulin secretion correlated with increases in cytosolic calcium, but not with changes in NAD(P)H or the ATP/ADP ratio. These data suggest a role for mtGTP in controlling pancreatic GSIS through modulation of mitochondrial metabolism, possibly involving mitochondrial calcium. Furthermore, in light of its tight coupling to TCA oxidation rates, mtGTP production may serve as an important molecular signal of TCA-cycle activity.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
succinate metabolic process  IDA 2306915; 2306915; 2306915 RGD 
succinyl-CoA metabolic process  IDA 2306915; 2306915; 2306915 RGD 
tricarboxylic acid cycle  IDA 2306915; 2306915; 2306915 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
succinate-CoA ligase (ADP-forming) activity  IDA 2306915; 2306915 RGD 
succinate-CoA ligase (GDP-forming) activity  IDA 2306915; 2306915 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Sucla2  (succinate-CoA ligase ADP-forming subunit beta)
Suclg1  (succinate-CoA ligase GDP/ADP-forming subunit alpha)
Suclg2  (succinate-CoA ligase GDP-forming subunit beta)

Genes (Mus musculus)
Sucla2  (succinate-Coenzyme A ligase, ADP-forming, beta subunit)
Suclg1  (succinate-CoA ligase, GDP-forming, alpha subunit)
Suclg2  (succinate-Coenzyme A ligase, GDP-forming, beta subunit)

Genes (Homo sapiens)
SUCLA2  (succinate-CoA ligase ADP-forming subunit beta)
SUCLG1  (succinate-CoA ligase GDP/ADP-forming subunit alpha)
SUCLG2  (succinate-CoA ligase GDP-forming subunit beta)


Additional Information