Metabolic Effects of Selective Deletion of Group VIA Phospholipase A2 from Macrophages or Pancreatic Islet Beta-Cells.

ABSTRACT: To examine the role of group VIA phospholipase A2 (iPLA2?) in specific cell lineages in insulin secretion and insulin action, we prepared mice with a selective iPLA2? deficiency in cells of myelomonocytic lineage, including macrophages (MØ-iPLA2?-KO), or in insulin-secreting ?-cells (?-Cell-iPLA2?-KO), respectively. MØ-iPLA2?-KO mice exhibited normal glucose tolerance when fed standard chow and better glucose tolerance than floxed-iPLA2? control mice after consuming a high-fat diet (HFD). MØ-iPLA2?-KO mice exhibited normal glucose-stimulated insulin secretion (GSIS) in vivo and from isolated islets ex vivo compared to controls. Male MØ-iPLA2?-KO mice exhibited enhanced insulin responsivity vs. controls after a prolonged HFD. In contrast, ?-cell-iPLA2?-KO mice exhibited impaired glucose tolerance when fed standard chow, and glucose tolerance deteriorated further when introduced to a HFD. ?-Cell-iPLA2?-KO mice exhibited impaired GSIS in vivo and from isolated islets ex vivo vs. controls. ?-Cell-iPLA2?-KO mice also exhibited an enhanced insulin responsivity compared to controls. These findings suggest that MØ iPLA2? participates in HFD-induced deterioration in glucose tolerance and that this mainly reflects an effect on insulin responsivity rather than on insulin secretion. In contrast, ?-cell iPLA2? plays a role in GSIS and also appears to confer some protection against deterioration in ?-cell functions induced by a HFD.

SUBMITTER: Turk J 

PROVIDER: S-EPMC7602969 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature