Department of Nephrology, Renmin Hospital of Wuhan University, China.
Prostaglandins Other Lipid Mediat. 2011 Aug;95(1-4):1-10. doi: 10.1016/j.prostaglandins.2011.06.001. Epub 2011 Jul 3.
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 30 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 E(2) (PGE(2)), 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.
花生四烯酸（AA）可被环加氧酶（COX）、脂加氧酶（LOX）和细胞色素 P450（CYP）代谢为类二十烷酸，参与多种疾病，包括 1 型和 2 型糖尿病。在过去的 30 年中，有证据表明类二十烷酸在控制胰岛β细胞功能和破坏方面具有重要功能。COX 途径的 AA 代谢物，特别是前列腺素 E2（PGE2），似乎是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。一些精心设计的研究有助于理清 12-LOX 类二十烷酸在胰岛β细胞细胞因子介导的炎症中的重要性。CYP 类二十烷酸在糖尿病中的作用尚未得到探索。最近的一项研究表明，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（EETs）、CYP 类二十烷酸的水平，可改善糖尿病中β细胞的功能并减少β细胞凋亡。在这篇综述中，我们总结了这些类二十烷酸途径在糖尿病及其并发症中的最新发现。我们还讨论了在每条途径中使用靶向基因缺失和特定酶抑制剂的动物模型的发展，以确定治疗糖尿病及其并发症的潜在靶点。
