Role of extracellular proton-sensing OGR1 in regulation of insulin secretion and pancreatic β-cell functions

Endocrine Journal

Fumikazu Okajima¹  Takashi Nakakura¹  Chihiro Mogi¹ 

[1] Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan

关键词: Proton-sensing GPCRs;    OGR1;    Insulin secretion;    Pancreatic β-cell;   

DOI  :  10.1507/endocrj.EJ13-0380

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(74)Cited-By(4)Insulin secretion with respect to pH environments has been investigated for a long time but its mechanism remains largely unknown.Extracellular pH is usually maintained at around 7.4 and, its change has been thought to occur in non-physiological situations.Acidification takes place under ischemic and inflammatory microenvironments, where stimulation of anaerobic glycolysis results in the production of lactic acid.In addition to ionotropic ion channels, such as transient receptor potential V1 (TRPV1) and acid-sensing ion channels (ASICs), metabotropic proton-sensing G protein-coupled receptors (GPCRs) have also been identified recently as proton-sensing machineries.While ionotropic ion channels usually sense strong acidic pH, proton-sensing GPCRs sense pH of 7.6 to 6.0 and have been shown to mediate a variety of biological actions in neutral and mildly acidic pH environments.Studies with receptor knockout mice have revealed that proton-sensing receptors, including ovarian cancer G protein-coupled receptor 1 (OGR1), a proton-sensing GPCRs, play a role in the regulation of insulin secretion and glucose metabolism under physiological conditions.Small molecule 3,5-disubstituted isoxazoles have recently been identified as OGR1 agonists working at neutral pH and have been shown to stimulate pancreatic β-cell differentiation and insulin synthesis.Thus, proton-sensing OGR1 may be an important player for insulin secretion and a potential target for improving β-cell function.

【 授权许可】

Unknown