Arachidonic acid signaling is involved in the mechanism of imidazoline-induced KATP channel-independent stimulation of insulin secretion

V. V. Sharoyko, I. I. Zaitseva, B. Leibiger, S. Efendić, P. O. Berggren, S. V. Zaitsev

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The mechanism by which the novel, pure glucose-dependent insulinotropic, imidazoline derivative BL11282 promotes insulin secretion in pancreatic islets has been investigated. The roles of KATP channels, α2-adrenoreceptors, the I1-receptor- phosphatidylcholine-specific phospholipase (PC-PLC) pathway and arachidonic acid signaling in BL11282 potentiation of insulin secretion in pancreatic islets were studied. Using SUR1(-/-) deficient mice, the previous notion that the insulinotropic activity of BL11282 is not related to its interaction with KATP channels was confirmed. Insulinotropic activity of BL11282 was not related to its effect on α2-adrenoreceptors, I 1-imidazoline receptors or PC-PLC. BL11282 significantly increased [3H]arachidonic acid production. This effect was abolished in the presence of the iPLA2 inhibitor, bromoenol lactone. The data suggest that potentiation of glucose-induced insulin release by BL11282, which is independent of concomitant changes in cytoplasmic free Ca2+ concentration, involves release of arachidonic acid by iPLA2 and its metabolism to epoxyeicosatrienoic acids through the cytochrome P-450 pathway.

Original languageEnglish
Pages (from-to)2985-2993
Number of pages9
JournalCellular and Molecular Life Sciences
Volume64
Issue number22
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Fingerprint

BL 11282
Imidazolines
KATP Channels
Arachidonic Acid
Insulin
Islets of Langerhans
Glucose
Phospholipases
Phosphatidylcholines
Metabolism
Cytochrome P-450 Enzyme System

Keywords

  • Arachidonic acid
  • BL11282
  • Calcium-independent phospholipase A
  • Cytochrome P-450
  • Imidazolines
  • Insulin secretion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Arachidonic acid signaling is involved in the mechanism of imidazoline-induced KATP channel-independent stimulation of insulin secretion. / Sharoyko, V. V.; Zaitseva, I. I.; Leibiger, B.; Efendić, S.; Berggren, P. O.; Zaitsev, S. V.

In: Cellular and Molecular Life Sciences, Vol. 64, No. 22, 01.11.2007, p. 2985-2993.

Research output: Contribution to journalArticle

Sharoyko, V. V. ; Zaitseva, I. I. ; Leibiger, B. ; Efendić, S. ; Berggren, P. O. ; Zaitsev, S. V. / Arachidonic acid signaling is involved in the mechanism of imidazoline-induced KATP channel-independent stimulation of insulin secretion. In: Cellular and Molecular Life Sciences. 2007 ; Vol. 64, No. 22. pp. 2985-2993.
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