New Insights into Beta-Cell GLP-1 Receptor and cAMP Signaling

J Mol Biol. 2020 Mar 6;432(5):1347-1366. doi: 10.1016/j.jmb.2019.08.009. Epub 2019 Aug 22.

Abstract

Harnessing the translational potential of the GLP-1/GLP-1R system in pancreatic beta cells has led to the development of established GLP-1R-based therapies for the long-term preservation of beta cell function. In this review, we discuss recent advances in the current research on the GLP-1/GLP-1R system in beta cells, including the regulation of signaling by endocytic trafficking as well as the application of concepts such as signal bias, allosteric modulation, dual agonism, polymorphic receptor variants, spatial compartmentalization of cAMP signaling and new downstream signaling targets involved in the control of beta cell function.

Keywords: GLP-1 receptor; beta cell survival; cAMP signaling; incretin; insulin secretion; pancreatic beta cell.

Publication types

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

MeSH terms

  • Animals
  • Cyclic AMP / metabolism*
  • Diabetes Mellitus, Type 2* / pathology
  • Diabetes Mellitus, Type 2* / therapy
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide-1 Receptor* / genetics
  • Glucagon-Like Peptide-1 Receptor* / metabolism
  • Humans
  • Incretins / metabolism
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells* / metabolism
  • Insulin-Secreting Cells* / pathology
  • Polymorphism, Single Nucleotide
  • Signal Transduction

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • Insulin
  • Glucagon-Like Peptide 1
  • Cyclic AMP