Regulated expression and function of the GABA B receptor in human pancreatic beta cell line and islets

Sci Rep. 2020 Aug 10;10(1):13469. doi: 10.1038/s41598-020-69758-6.

Abstract

G protein-coupled receptors are seven transmembrane signaling molecules that are involved in a wide variety of physiological processes. They constitute a large protein family of receptors with almost 300 members detected in human pancreatic islet preparations. However, the functional role of these receptors in pancreatic islets is unknown in most cases. We generated a new stable human beta cell line from neonatal pancreas. This cell line, named ECN90 expresses both subunits (GABBR1 and GABBR2) of the metabotropic GABAB receptor compared to human islet. In ECN90 cells, baclofen, a specific GABAB receptor agonist, inhibits cAMP signaling causing decreased expression of beta cell-specific genes such as MAFA and PCSK1, and reduced insulin secretion. We next demonstrated that in primary human islets, GABBR2 mRNA expression is strongly induced under cAMP signaling, while GABBR1 mRNA is constitutively expressed. We also found that induction and activation of the GABAB receptor in human islets modulates insulin secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Baclofen / pharmacology
  • Cell Line
  • GABA-B Receptor Agonists / pharmacology
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / physiology
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / physiology
  • Pancreas / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, GABA-B / genetics*
  • Receptors, GABA-B / metabolism
  • Signal Transduction
  • gamma-Aminobutyric Acid / metabolism

Substances

  • GABA-B Receptor Agonists
  • Insulin
  • Receptors, G-Protein-Coupled
  • Receptors, GABA-B
  • gamma-Aminobutyric Acid
  • Baclofen