Emerging roles of GPER in diabetes and atherosclerosis

Trends Endocrinol Metab. 2015 Apr;26(4):185-92. doi: 10.1016/j.tem.2015.02.003. Epub 2015 Mar 9.


The G protein-coupled estrogen receptor (GPER) is a 7-transmembrane receptor implicated in rapid estrogen signaling. Originally cloned from vascular endothelial cells, GPER plays a central role in the regulation of vascular tone and cell growth as well as lipid and glucose homeostasis. This review highlights our knowledge of the physiological and pathophysiological functions of GPER in the pancreas, peripheral and immune tissues, and the arterial vasculature. Recent findings on its roles in obesity, diabetes, and atherosclerosis, including GPER-dependent regulation of lipid metabolism and inflammation, are presented. The therapeutic potential of targeting GPER-dependent pathways in chronic diseases such as coronary artery disease and diabetes and in the context of menopause is also discussed.

Keywords: GPER; atherosclerosis; diabetes; estrogen receptor; rapid signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Obesity Agents / therapeutic use
  • Atherosclerosis / drug therapy
  • Atherosclerosis / immunology
  • Atherosclerosis / metabolism*
  • Cardiovascular Agents / therapeutic use
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / metabolism*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Ligands
  • Lipid Metabolism* / drug effects
  • Models, Biological*
  • Molecular Targeted Therapy
  • Obesity / drug therapy
  • Obesity / immunology
  • Obesity / metabolism*
  • Organ Specificity
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / metabolism*
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction* / drug effects


  • Anti-Obesity Agents
  • Cardiovascular Agents
  • GPER1 protein, human
  • Hypoglycemic Agents
  • Ligands
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled