The dual role of group V secretory phospholipase A 2 in pancreatic β-cells

Abstract

Purpose

Group X (GX) and group V (GV) secretory phospholipase A₂ (sPLA₂) potently release arachidonic acid (AA) from the plasma membrane of intact cells. We previously demonstrated that GX sPLA₂ negatively regulates glucose-stimulated insulin secretion (GSIS) by a prostaglandin E2 (PGE2)-dependent mechanism. In this study we investigated whether GV sPLA₂ similarly regulates GSIS.

Methods

GSIS and pancreatic islet-size were assessed in wild-type (WT) and GV sPLA₂-knock out (GV KO) mice. GSIS was also assessed ex vivo in isolated islets and in vitro using MIN6 pancreatic beta cell lines with or without GV sPLA₂ overexpression or silencing.

Results

GSIS was significantly decreased in islets isolated from GV KO mice compared to WT mice and in MIN6 cells with siRNA-mediated GV sPLA₂ suppression. MIN6 cells overexpressing GV sPLA₂ (MIN6-GV) showed a significant increase in GSIS compared to control cells. Though the amount of AA released into the media by MIN6-GV cells was significantly higher, PGE2 production was not enhanced or cAMP content decreased compared to control MIN6 cells. Surprisingly, GV KO mice exhibited a significant increase in plasma insulin levels following i.p. injection of glucose compared to WT mice. This increase in GSIS in GV KO mice was associated with a significant increase in pancreatic islet size and number of proliferating cells in β-islets compared to WT mice.

Conclusions

Deficiency of GV sPLA₂ results in diminished GSIS in isolated pancreatic beta-cells. However, the reduced GSIS in islets lacking GV sPLA₂ appears to be compensated by increased islet mass in GV KO mice.

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