The dual role of group V secretory phospholipase A2 in pancreatic β-cells

Abstract

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. GSIS was significantly decreased in islets isolated from GV sPLA2-deficient (GV KO) mice compared to wild-type (WT) mice. Similarly, GSIS was significantly decreased in MIN6 cells, a murine pancreatic beta cell line with siRNA-mediated GV sPLA2 suppression. MIN6 cells overexpressing GV sPLA2 (MIN6-GV) showed a significant increase in GSIS compared to control cells. The amount of AA released into the media by MIN6-GV cells was significantly higher compared to control cells. However, MIN6-GV cells did not exhibit enhanced PGE2 production or decreased cAMP content 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. Thus, 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.

Secretory Phospholipase A2s in Insulin Resistance and Metabolism

“…Additionally, PLA2G5 overexpression in MIN6 cells enhanced GSIS and increased AA release into the media with no change in prostaglandin E2 (PGE2) abundance (58). In contrast to the studies with isolated islets, the GSIS of Pla2g5 -/mice was increased compared to WT mice (58). The elevated GSIS was attributed to increased pancreatic islet size and number of proliferating cells in the pancreatic b-islets of the Pla2g5 KO mice.…”

“…GSIS is decreased in isolated pancreatic islets from PLA2G5 knockout mice and in pancreatic MIN6 cells following siRNA-mediated PLA2G5 knockdown (58). Additionally, PLA2G5 overexpression in MIN6 cells enhanced GSIS and increased AA release into the media with no change in prostaglandin E2 (PGE2) abundance (58). In contrast to the studies with isolated islets, the GSIS of Pla2g5 -/mice was increased compared to WT mice (58).…”

“…The role of PLA2G5 in glucose-stimulated insulin secretion (GSIS) is complex. GSIS is decreased in isolated pancreatic islets from PLA2G5 knockout mice and in pancreatic MIN6 cells following siRNA-mediated PLA2G5 knockdown (58). Additionally, PLA2G5 overexpression in MIN6 cells enhanced GSIS and increased AA release into the media with no change in prostaglandin E2 (PGE2) abundance (58).…”

Harmful and protective roles of group V phospholipase A2: Current perspectives and future directions

“…Mechanistically, OA and to a lesser extent LA released from hyperlipidemic LDL by adipocyte-derived Pla2g5, attenuated (or counteracted) palmitate-induced M1 macrophage polarization in adipose tissue, resulting in protective effects in obesity and associated inflammation. Consistently, increased glucose-stimulated insulin secretion (GSIS) was reported in non-obese Pla2g5-null mice [82]. Interestingly, Pla2g2e-null mice had reduced HFD-induced obesity, and reduced phospholipids and cholesterol in plasma lipoproteins [44].…”

Intestinal homeostasis and inflammation: Gut microbiota at the crossroads of pancreas–intestinal barrier axis

“…Based on a cluster analysis of varying propeptide sequences, specific disulfide bonds, and C-terminal extension sequences of these subtypes, human sPLA 2 is divided into three groups: type I/II/V/X, type III, and type XII [84]. Evidence suggests that subtypes IB, IID, V, X, and XIIB are expressed in the pancreas [26,85,86].…”