title: Eicosanoids, β-cell function, and diabetes.
abstract: 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.
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Luo
authors.forename: Mong-Heng
authors.initials: MH
authors.lastname: Wang
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D015777:Eicosanoids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008084:Lipoxygenase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
chemical_list: D015777:Eicosanoids; D015525:Fatty Acids, Omega-3; D003577:Cytochrome P-450 Enzyme System; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases