Glucose-inhibition of glucagon secretion involves activation of GABA(A)-receptor chloride channels

P. Rorsman, P. O. Berggren, K. Bokvist, H. Ericson, H. Mohler, C. G. Ostenson, P. A. Smith

Research output: Contribution to journalArticle

324 Citations (Scopus)

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 α2 cells. The mechanisms involved, however, remain unknown. Electrophysiological studies have demonstrated that α2 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 γ-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 β cells. We now describe a mechnism whereby GABA, co-secreted with insulin from β-cells, may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABA(A)-receptor Cl- channels in α2 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.

Original languageEnglish
Pages (from-to)233-236
Number of pages4
JournalNature
Volume341
Issue number6239
StatePublished - Jan 1 1989
Externally publishedYes

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Chloride Channels
GABA-A Receptors
Glucagon
Glucose
Insulin
Islets of Langerhans
gamma-Aminobutyric Acid
Action Potentials
Pancreatic Hormones
Aminobutyrates
Hyperglycemia
Neurotransmitter Agents
Blood Glucose
Central Nervous System

ASJC Scopus subject areas

  • General

Cite this

Rorsman, P., Berggren, P. O., Bokvist, K., Ericson, H., Mohler, H., Ostenson, C. G., & Smith, P. A. (1989). Glucose-inhibition of glucagon secretion involves activation of GABA(A)-receptor chloride channels. Nature, 341(6239), 233-236.

Glucose-inhibition of glucagon secretion involves activation of GABA(A)-receptor chloride channels. / Rorsman, P.; Berggren, P. O.; Bokvist, K.; Ericson, H.; Mohler, H.; Ostenson, C. G.; Smith, P. A.

In: Nature, Vol. 341, No. 6239, 01.01.1989, p. 233-236.

Research output: Contribution to journalArticle

Rorsman, P, Berggren, PO, Bokvist, K, Ericson, H, Mohler, H, Ostenson, CG & Smith, PA 1989, 'Glucose-inhibition of glucagon secretion involves activation of GABA(A)-receptor chloride channels', Nature, vol. 341, no. 6239, pp. 233-236.
Rorsman P, Berggren PO, Bokvist K, Ericson H, Mohler H, Ostenson CG et al. Glucose-inhibition of glucagon secretion involves activation of GABA(A)-receptor chloride channels. Nature. 1989 Jan 1;341(6239):233-236.
Rorsman, P. ; Berggren, P. O. ; Bokvist, K. ; Ericson, H. ; Mohler, H. ; Ostenson, C. G. ; Smith, P. A. / Glucose-inhibition of glucagon secretion involves activation of GABA(A)-receptor chloride channels. In: Nature. 1989 ; Vol. 341, No. 6239. pp. 233-236.
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