The influence of gamma-aminobutyric acid on hormone release by the mouse and rat endocrine pancreas.
The present study was aimed at localizing gamma-aminobutyric acid (GABA) and its enzyme of synthesis, glutamic acid decarboxylase (GAD), in the mouse pancreas by immunocytochemical methods. The influence of GABA on hormone release was also studied with normal mouse and rat islets and the isolated perfused rat pancreas. Particular attention was paid to glucagon release to test a recent hypothesis suggesting that GABA mediates the still unexplained glucose-induced inhibition of glucagon release. GABA and GAD were identified only in islet cells and never in the exocrine tissue. Exogenous GABA, baclofen (agonist of GABAB receptors), muscimol (agonist of GABAA receptors), or bicuculline (antagonist of GABAA receptors) did not affect insulin and somatostatin release by isolated mouse or rat islets. GABA was also without effect on glucose-induced electrical activity in mouse B-cells. Glucagon secretion by mouse islets was only slightly inhibited (approximately 20%) by GABA. Since muscimol had a similar effect, and baclofen was ineffective, the inhibition by GABA probably involves GABAA receptor activation. Bicuculline, however, did not antagonize the inhibitory effects of GABA and muscimol, probably because the antagonist alone also decreased glucagon secretion. In contrast to GABA, low (3 mM) and high (20 mM) concentrations of glucose strongly inhibited (approximately 50-65%) glucagon release; this inhibition was not prevented by bicuculline. Similar results were obtained with the perfused rat pancreas; muscimol slightly inhibited glucagon release under various conditions, and bicuculline did not reverse the strong inhibition produced by 16.7 mM glucose. In conclusion, GABA does not affect insulin and somatostatin secretion, but inhibits A-cells, probably by acting on GABAA receptors. It is unlikely, however, that this small inhibitory effect can account for the inhibition of glucagon release produced by glucose.
Gilon
P
P
Unité de Diabétologie et Nutrition, University of Louvain, Faculty of Medicine, Brussels, Belgium.
Bertrand
G
G
Loubatières-Mariani
M M
MM
Remacle
C
C
Henquin
J C
JC
D000818:Animals; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials; D051379:Mice; D008815:Mice, Inbred Strains; D010187:Pancreatic Hormones / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology
D007328:Insulin; D010187:Pancreatic Hormones; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D005934:Glucagon; D005968:Glutamate Decarboxylase