Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels

Nature. 1989 Sep 21;341(6239):233-6. doi: 10.1038/341233a0.

Abstract

The endocrine part of the pancreas plays a central role in blood-glucose regulation. It is well established that an elevation of glucose concentration reduces secretion of the hyperglycaemia-associated hormone glucagon from pancreatic alpha 2 cells. The mechanisms involved, however, remain unknown. Electrophysiological studies have demonstrated that alpha 2 cells generate Ca2+-dependent action potentials. The frequency of these action potentials, which increases under conditions that stimulate glucagon release, is not affected by glucose or insulin. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is present in the endocrine part of the pancreas at concentrations comparable to those encountered in the central nervous system, and co-localizes with insulin in pancreatic beta cells. We now describe a mechanism whereby GABA, co-secreted with insulin from beta cells, may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABAA-receptor Cl- channels in alpha 2 cells. These observations provide a model for feedback regulation of glucagon release, which may be of significance for the understanding of the hypersecretion of glucagon frequently associated with diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bicuculline / pharmacology
  • Chloride Channels
  • Chlorides / physiology*
  • Electric Conductivity
  • Glucagon / metabolism*
  • Glucose / pharmacology*
  • Guinea Pigs
  • In Vitro Techniques
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology*
  • Membrane Potentials
  • Membrane Proteins / physiology*
  • Receptors, GABA-A / physiology*
  • Secretory Rate / drug effects
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / physiology*

Substances

  • Chloride Channels
  • Chlorides
  • Membrane Proteins
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Glucagon
  • Glucose
  • Bicuculline