Eicosanoids, β-cell function, and diabetes.
Eicosanoids, β-cell function, and diabetes.
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DOI：
10.1016/j.prostaglandins.2011.06.001
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发表时间：
2011-08
影响因子：
2.9
通讯作者：
Wang MH
中科院分区：
文献类型：
--
作者：
Luo P;Wang MH
花生四烯酸（AA）被环氧合酶（考克斯）、脂氧合酶（LOX）和细胞色素P450（CYP）酶代谢为类花生酸，其参与多种疾病，包括1型和2型糖尿病。在过去的三十年中，已经积累了证据表明类二十烷酸在控制胰腺β细胞功能和破坏中的重要功能。考克斯途径的AA代谢产物，尤其是前列腺素E2（PGE 2），是β细胞功能障碍和破坏的重要因素，参与了糖尿病及其并发症的发病机制。几项出色的研究有助于整理出12-LOX类花生酸在胰腺β细胞中甘氨酸介导的炎症中的重要性。类花生酸在糖尿病中的作用尚待探索。最近的出版物已经证明，通过抑制或删除可溶性环氧化物水解酶（sEH）来稳定环氧二十碳三烯酸（E3）、类二十烷酸的水平，改善了糖尿病中的β细胞功能并减少了β细胞凋亡。在这篇综述中，我们总结了最近的研究结果涉及这些类花生酸途径在糖尿病及其并发症。我们还讨论了动物模型的发展与靶向基因缺失和特定的酶抑制剂在每一个途径，以确定潜在的目标，治疗糖尿病及其并发症。
Arachidonic acid (AA) is metabolized by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes into eicosanoids, which are involved in diverse diseases, including type 1 and type 2 diabetes. During the last thirty years, evidence has been accumulated that suggests important functions for eicosanoids in the control of pancreatic β-cell function and destruction. AA metabolites of the COX pathway, especially prostaglandin E2 (PGE2), appear to be significant factors to β-cell dysfunction and destruction, participating in the pathogenesis of diabetes and its complications. Several elegant studies have contributed to the sorting out of the importance of 12-LOX eicosanoids in cytokine-mediated inflammation in pancreatic β cells. The role of CYP eicosanoids in diabetes is yet to be explored. A recent publication has demonstrated that stabilizing the levels of epoxyeicosatrienoic acids (EETs), CYP eicosanoids, by inhibiting or deleting soluble epoxide hydrolase (sEH) improves β-cell function and reduces β-cell apoptosis in diabetes. In this review we summarize recent findings implicating these eicosanoid pathways in diabetes and its complications. We also discuss the development of animal models with targeted gene deletion and specific enzymatic inhibitors in each pathway to identify potential targets for the treatment of diabetes and its complications.