Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels.
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.
Rorsman
P
P
Department of Medical Physics, Gothenburg University, Sweden.
Berggren
P O
PO
Bokvist
K
K
Ericson
H
H
Möhler
H
H
Ostenson
C G
CG
Smith
P A
PA
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology*; D004553:Electric Conductivity; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005934:Glucagon; D005947:Glucose; D001640:Bicuculline