Abstract
Fuel secretagogues induce hydrolysis of esterified arachidonic acid from pancreatic islet cell phospholipids and accumulation of nonesterified arachidonate at concentrations up to 35 μM. Exogenous arachidonate (5-30 μM) amplifies depolarization-induced insulin secretion from islets. Fuel secretagogueinduced hydrolysis of arachidonate from islet phospholipids occurs in Ca2+-free medium, suggesting the possible involvement of a Ca2+-independent phospholipase. In the companion paper [Gross et al. (1993) Biochemistry (preceding paper in this issue)], we demonstrated that the major islet phospholipase A2 is Ca2+-independent, ATP-stimulated, and inhibited by the haloenol lactone suicide substrate (HELSS) (E)- 6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one. Here we demonstrate that HELSS suppressed both release of the arachidonate metabolite prostaglandin E2 and insulin secretion from islets stimulated with d-glucose and the muscarinic agonist carbachol. Both prostaglandin E2 release and insulin secretion were suppressed with similar concentration profiles and time courses. Islet oxidation of [14C]- glucose to [14C]CO2, activities of islet lactate dehydrogenase and alanine and aspartate aminotransferases, and carbachol-induced inositol phosphate accumulation in islets were all unaffected by HELSS. Depolarization of isolated β-cells with 40mM KCl induced a rise in cytosolic [Ca2+] that was also unaffected by HELSS. In contrast, the 17 mM d-glucose-induced rise in β-cell [Ca2+] was inhibited by HELSS in a concentration-dependent manner, but that induced by exogenous arachidonate (15 μM) was not. These results suggest that fuel secretagogues activate the islet Ca2+-independent phospholipase A2, resulting in release of nonesterified arachidonate, which facilitates Ca2+ entry into β-cells and promotes insulin secretion.
Original language | English (US) |
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Pages (from-to) | 337-346 |
Number of pages | 10 |
Journal | Biochemistry |
Volume | 32 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 1993 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry