RGD Reference Report - Adenovirus-mediated overexpression of liver carnitine palmitoyltransferase I in INS1E cells: effects on cell metabolism and insulin secretion. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Adenovirus-mediated overexpression of liver carnitine palmitoyltransferase I in INS1E cells: effects on cell metabolism and insulin secretion.

Authors: Rubi, B  Antinozzi, PA  Herrero, L  Ishihara, H  Asins, G  Serra, D  Wollheim, CB  Maechler, P  Hegardt, FG 
Citation: Rubi B, etal., Biochem J 2002 May 15;364(Pt 1):219-26.
RGD ID: 1298597
Pubmed: PMID:11988095   (View Abstract at PubMed)
PMCID: PMC1222564   (View Article at PubMed Central)

Lipid metabolism in the beta-cell is critical for the regulation of insulin secretion. Pancreatic beta-cells chronically exposed to fatty acids show higher carnitine palmitoyltransferase I (CPT I) protein levels, higher palmitate oxidation rates and an altered insulin response to glucose. We examined the effect of increasing CPT I levels on insulin secretion in cultured beta-cells. We prepared a recombinant adenovirus containing the cDNA for the rat liver isoform of CPT I. The overexpression of CPT I in INS1E cells caused a more than a 5-fold increase in the levels of CPT I protein (detected by Western blotting), a 6-fold increase in the CPT activity, and an increase in fatty acid oxidation at 2.5 mM glucose (1.7-fold) and 15 mM glucose (3.1-fold). Insulin secretion was stimulated in control cells by 15 mM glucose or 30 mM KCl. INS1E cells overexpressing CPT I showed lower insulin secretion on stimulation with 15 mM glucose (-40%; P<0.05). This decrease depended on CPT I activity, since the presence of etomoxir, a specific inhibitor of CPT I, in the preincubation medium normalized the CPT I activity, the fatty-acid oxidation rate and the insulin secretion in response to glucose. Exogenous palmitate (0.25 mM) rescued glucose-stimulated insulin secretion (GSIS) in CPT I-overexpressing cells, indicating that the mechanism of impaired GSIS was through the depletion of a critical lipid. Depolarizing the cells with KCl or intermediary glucose concentrations (7.5 mM) elicited similar insulin secretion in control cells and cells overexpressing CPT I. Glucose-induced ATP increase, glucose metabolism and the triacylglycerol content remained unchanged. These results provide further evidence that CPT I activity regulates insulin secretion in the beta-cell. They also indicate that up-regulation of CPT I contributes to the loss of response to high glucose in beta-cells exposed to fatty acids.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of fatty acid oxidation  IMP 1298597 RGD 
regulation of insulin secretion  IMP 1298597 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
carnitine O-palmitoyltransferase activity  IDA 1298597 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cpt1a  (carnitine palmitoyltransferase 1A)


Additional Information