RT Journal Article
SR Electronic
T1 Glucose Inhibition of Glucagon Secretion From Rat α-Cells Is Mediated by GABA Released From Neighboring β-Cells
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 1038
OP 1045
DO 10.2337/diabetes.53.4.1038
VO 53
IS 4
A1 Wendt, Anna
A1 Birnir, Bryndis
A1 Buschard, Karsten
A1 Gromada, Jesper
A1 Salehi, Albert
A1 Sewing, Sabine
A1 Rorsman, Patrik
A1 Braun, Matthias
YR 2004
UL http://diabetes.diabetesjournals.org/content/53/4/1038.abstract
AB γ-Aminobutyric acid (GABA) has been proposed to function as a paracrine signaling molecule in islets of Langerhans. We have shown that rat β-cells release GABA by Ca2+-dependent exocytosis of synaptic-like microvesicles. Here we demonstrate that GABA thus released can diffuse over sufficient distances within the islet interstitium to activate GABAA receptors in neighboring cells. Confocal immunocytochemistry revealed the presence of GABAA receptors in glucagon-secreting α-cells but not in β- and δ-cells. RT-PCR analysis detected transcripts of α1 and α4 as well as β1–3 GABAA receptor subunits in purified α-cells but not in β-cells. In whole-cell voltage-clamp recordings, exogenous application of GABA activated Cl− currents in α-cells. The GABAA receptor antagonist SR95531 was used to investigate the effects of endogenous GABA (released from β-cells) on pancreatic islet hormone secretion. The antagonist increased glucagon secretion at 1 mmol/l glucose twofold and completely abolished the inhibitory action of 20 mmol/l glucose on glucagon release. Basal and glucose-stimulated secretion of insulin and somatostatin were unaffected by SR95531. The L-type Ca2+ channel blocker isradipine evoked a paradoxical stimulation of glucagon secretion. This effect was not observed in the presence of SR95531, and we therefore conclude that isradipine stimulates glucagon secretion by inhibition of GABA release.