To examine the role of group VIA phospholipase A₂ (iPLA₂β) in specific cell lineages in insulin secretion and insulin action, we prepared mice with a selective iPLA₂β deficiency in cells of myelomonocytic lineage, including macrophages (MØ-iPLA₂β-KO), or in insulin-secreting β-cells (β-Cell-iPLA₂β-KO), respectively. MØ-iPLA₂β-KO mice exhibited normal glucose tolerance when fed standard chow and better glucose tolerance than floxed-iPLA₂β control mice after consuming a high-fat diet (HFD). MØ-iPLA₂β-KO mice exhibited normal glucose-stimulated insulin secretion (GSIS) in vivo and from isolated islets ex vivo compared to controls. Male MØ-iPLA₂β-KO mice exhibited enhanced insulin responsivity vs. controls after a prolonged HFD. In contrast, β-cell-iPLA₂β-KO mice exhibited impaired glucose tolerance when fed standard chow, and glucose tolerance deteriorated further when introduced to a HFD. β-Cell-iPLA₂β-KO mice exhibited impaired GSIS in vivo and from isolated islets ex vivo vs. controls. β-Cell-iPLA₂β-KO mice also exhibited an enhanced insulin responsivity compared to controls. These findings suggest that MØ iPLA₂β 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, β-cell iPLA₂β plays a role in GSIS and also appears to confer some protection against deterioration in β-cell functions induced by a HFD.

中文翻译：

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从巨噬细胞或胰岛 β 细胞中选择性删除 VIA 组磷脂酶 A2 的代谢效应

为了检查 VIA 组磷脂酶 A ₂ (iPLA ₂ β) 在特定细胞谱系中对胰岛素分泌和胰岛素作用的作用，我们在包括巨噬细胞 (MØ-iPLA ₂ β ) 在内的骨髓单核细胞谱系细胞中制备了选择性 iPLA ₂ β 缺陷的小鼠-KO) 或分泌胰岛素的 β 细胞 (β-Cell-iPLA ₂ β-KO)。MØ-iPLA ₂ β-KO 小鼠在食用标准食物时表现出正常的葡萄糖耐量，并且在食用高脂肪饮食 (HFD) 后比 floxed-iPLA _{2 β 对照小鼠具有更好的葡萄糖耐量。}MØ-iPLA ₂与对照相比，β-KO 小鼠在体内和离体离体胰岛表现出正常的葡萄糖刺激的胰岛素分泌 (GSIS)。与对照组相比，雄性 MØ-iPLA ₂ β-KO 小鼠在长时间的 HFD 后表现出增强的胰岛素反应性。相比之下，β-cell-iPLA ₂ β-KO 小鼠在喂食标准食物时表现出葡萄糖耐量受损，并且当引入 HFD 时葡萄糖耐量进一步恶化。与对照相比， β-Cell-iPLA ₂ β-KO 小鼠在体内和离体胰岛的 GSIS 受损。与对照组相比， β-Cell-iPLA ₂ β-KO 小鼠也表现出增强的胰岛素反应性。这些发现表明 MØ iPLA ₂β 参与 HFD 诱导的葡萄糖耐量恶化，这主要反映了对胰岛素反应性的影响，而不是对胰岛素分泌的影响。相比之下，β-cell iPLA ₂ β 在 GSIS 中发挥作用，并且似乎还可以对 HFD 诱导的 β-cell 功能恶化提供一些保护。