The EP3 Receptor/Gz Signaling Axis as a Therapeutic Target for Diabetes and Cardiovascular Disease

AAPS J. 2017 Sep;19(5):1276-1283. doi: 10.1208/s12248-017-0097-1. Epub 2017 Jun 5.

Abstract

Cardiovascular disease is a common co-morbidity found with obesity-linked type 2 diabetes. Current pharmaceuticals for these two diseases treat each of them separately. Yet, diabetes and cardiovascular disease share molecular signaling pathways that are increasingly being understood to contribute to disease pathophysiology, particularly in pre-clinical models. This review will focus on one such signaling pathway: that mediated by the G protein-coupled receptor, Prostaglandin E2 Receptor 3 (EP3), and its associated G protein in the insulin-secreting beta-cell and potentially the platelet, Gz. The EP3/Gz signaling axis may hold promise as a dual target for type 2 diabetes and cardiovascular disease.

Keywords: G proteins; GPCRs; cardiovascular disease; diabetes; prostaglandins; type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / etiology
  • Glucagon-Like Peptide-1 Receptor / physiology
  • Humans
  • Inflammation / etiology
  • Obesity / etiology
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • Receptors, Prostaglandin E, EP3 Subtype / antagonists & inhibitors*
  • Signal Transduction / drug effects

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Receptors, G-Protein-Coupled
  • Receptors, Prostaglandin E, EP3 Subtype