Bosma Karin J, Kaiser Cecilia E, Kimple Michelle E, Gannon Maureen
Department of Veterans Affairs, Tennessee Valley Authority, Nashville, TN 37212, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Metabolites. 2022 Apr 12;12(4):342. doi: 10.3390/metabo12040342.
Arachidonic acid (AA) is a polyunsaturated 20-carbon fatty acid present in phospholipids in the plasma membrane. The three primary pathways by which AA is metabolized are mediated by cyclooxygenase (COX) enzymes, lipoxygenase (LOX) enzymes, and cytochrome P450 (CYP) enzymes. These three pathways produce eicosanoids, lipid signaling molecules that play roles in biological processes such as inflammation, pain, and immune function. Eicosanoids have been demonstrated to play a role in inflammatory, renal, and cardiovascular diseases as well type 1 and type 2 diabetes. Alterations in AA release or AA concentrations have been shown to affect insulin secretion from the pancreatic beta cell, leading to interest in the role of AA and its metabolites in the regulation of beta-cell function and maintenance of beta-cell mass. In this review, we discuss the metabolism of AA by COX, LOX, and CYP, the roles of these enzymes and their metabolites in beta-cell mass and function, and the possibility of targeting these pathways as novel therapies for treating diabetes.
花生四烯酸（AA）是一种存在于质膜磷脂中的20碳多不饱和脂肪酸。花生四烯酸代谢的三条主要途径由环氧化酶（COX）、脂氧合酶（LOX）和细胞色素P450（CYP）介导。这三条途径产生类二十烷酸，即脂质信号分子，它们在炎症、疼痛和免疫功能等生物学过程中发挥作用。已证明类二十烷酸在炎症性疾病、肾脏疾病、心血管疾病以及1型和2型糖尿病中起作用。花生四烯酸释放或浓度的改变已显示会影响胰腺β细胞的胰岛素分泌，这引发了人们对花生四烯酸及其代谢产物在β细胞功能调节和β细胞量维持中作用的兴趣。在本综述中，我们讨论了COX、LOX和CYP对花生四烯酸代谢，这些酶及其代谢产物在β细胞量和功能中的作用，以及将这些途径作为治疗糖尿病新疗法的可能性。
