The mitochondrial citrate/isocitrate carrier plays a regulatory role in glucose-stimulated insulin secretion. (Articolo in rivista)

Type
Label
  • The mitochondrial citrate/isocitrate carrier plays a regulatory role in glucose-stimulated insulin secretion. (Articolo in rivista) (literal)
Anno
  • 2006-01-01T00:00:00+01:00 (literal)
Alternative label
  • J. W. Joseph, M. V. Jensen, O. Ilkayeva, F. Palmieri, C. Alárcon, C. J. Rhodes and C. B. Newgard (2006)
    The mitochondrial citrate/isocitrate carrier plays a regulatory role in glucose-stimulated insulin secretion.
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • J. W. Joseph, M. V. Jensen, O. Ilkayeva, F. Palmieri, C. Alárcon, C. J. Rhodes and C. B. Newgard (literal)
Pagina inizio
  • 35624 (literal)
Pagina fine
  • 32 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 281 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Laboratory of Biochemistry and Molecular Biology, Department of Pharmaco-Biology, University of Bari, Via Orabona 4, 70125 Bari, Italy (literal)
Titolo
  • The mitochondrial citrate/isocitrate carrier plays a regulatory role in glucose-stimulated insulin secretion. (literal)
Abstract
  • Glucose-stimulated insulin secretion (GSIS) is mediated in part by glucose metabolism-driven increases in ATP/ADP ratio, but by-products of mitochondrial glucose metabolism also play an important role. Here we investigate the role of the mitochondrial citrate/isocitrate carrier (CIC) in regulation of GSIS. Inhibition of CIC activity in INS-1-derived 832/13 cells or primary rat islets by the substrate analogue 1,2,3-benzenetricarboxylate (BTC) resulted in potent inhibition of GSIS, involving both first and second phase secretion. A recombinant adenovirus containing a CIC-specific siRNA (Ad-siCIC) dose-dependently reduced CIC expression in 832/13 cells and caused parallel inhibitory effects on citrate accumulation in the cytosol. Ad-siCIC treatment did not affect glucose utilization, glucose oxidation, or ATP/ADP ratio but did inhibit glucose incorporation into fatty acids and glucose-induced increases in NADPH/NADP(+) ratio relative to cells treated with a control siRNA virus (Ad-siControl). Ad-siCIC also inhibited GSIS in 832/13 cells, whereas overexpression of CIC enhanced GSIS and raised cytosolic citrate levels. In normal rat islets, Ad-siCIC treatment also suppressed CIC mRNA levels and inhibited GSIS. We conclude that export of citrate and/or isocitrate from the mitochondria to the cytosol is an important step in control of GSIS. (literal)
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