Metabolic Functions of G Protein-Coupled Receptors in Hepatocytes-Potential Applications for Diabetes and NAFLD

Biomolecules. 2020 Oct 15;10(10):1445. doi: 10.3390/biom10101445.

Abstract

G protein-coupled receptors (GPCRs) are cell surface receptors that mediate the function of extracellular ligands. Understanding how GPCRs work at the molecular level has important therapeutic implications, as 30-40% of the drugs currently in clinical use mediate therapeutic effects by acting on GPCRs. Like many other cell types, liver function is regulated by GPCRs. More than 50 different GPCRs are predicted to be expressed in the mouse liver. However, knowledge of how GPCRs regulate liver metabolism is limited. A better understanding of the metabolic role of GPCRs in hepatocytes, the dominant constituent cells of the liver, could lead to the development of novel drugs that are clinically useful for the treatment of various metabolic diseases, including type 2 diabetes, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In this review, we describe the functions of multiple GPCRs expressed in hepatocytes and their role in metabolic processes.

Keywords: G protein-coupled receptor; GPCR; NAFLD; NASH; diabetes; hepatocyte; liver; metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • GTP-Binding Proteins / genetics
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / therapeutic use
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Mice
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • Hypoglycemic Agents
  • Receptors, G-Protein-Coupled
  • GTP-Binding Proteins