The Role Of Prostaglandin E2Receptors In Insulin Secretion By Pancreatic Beta Cells

Glucose metabolism disorder is a serious threat to human health, and has closerelationship with the occurrence and development of cardiovascular and cerebrovasculardiseases, hypertension, obesity and metabolic syndrome and other diseases. In recentyears, the incidence of diabetes showed an upward trend. Interleukin-1β(IL-1β)has beenreported to have major inhibitory effects on β cell function, especially under conditions ofhigh glucose concentrations and prolonged exposure to this cytokine.IL-1β inducescyclooxygenase-2(COX-2) gene expression and PGE2synthesis in isletβ cells.The centraland peripheral actions of PGE2are mediated by four G protein-coupled receptor-typeprostanoid receptors (EP1R–EP4R). EP3is the most abundant EP receptor type in islets,liver, kidney, and epididymal fat.The EP3receptor decreased intracellular cyclic AMP(cAMP), blunting glucose-stimulated insulin secretion (GSIS). Also upregulated severalgenes involved in the synthesis of PGE2.But the specific mechanism is not entirely clear,so it is of great significance to do research on prevention and treatment of glucosemetabolism disorder-related diseases.ZBTB20is a newly identified zinc finger protein gene, which is expressed in avariety of tissues; however, its function is not well-understood yet. We generatedZBTB20global knockout mice, and found that the ZBTB20global knockout mice havesevere disorders of metabolism.Mice with β cell–specific knockout of Zbtb20had normal development of β cells buthad hyperglycemia, hypoinsulinemia, glucose intolerance, and impairedglucose-stimulated insulin secretion. Through fluorescent quantitative PCR, we find thatExpression of EP3was up-regulated in β cells with ZBTB20knockout or knockdown;impairments to glucose-stimulated insulin secretion were restored by inhibition of COX-2compared to control mice. Taken together, our data strongly suggest that up-regulated ofEP3plays an important role in glucose metabolism of β cell–specific knockout of Zbtb20and may represent a novel target for the treatment of Diabetes Mellitus.