Clonidine-displacing substance reduces glucagon secretion from mouse pancreatic alpha-cells by K(ATP)-channel-independent inhibition of exocytosis

Clonidine-displacing substance (CDS) is a potent stimulator of insulin release from pancreatic beta-cells and has been suggested to constitute the endogenous ligand for the islet imidazoline-binding site. Here we have explored the effects of CDS on glucagon release from mouse pancreatic alpha-cells....

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2001-10, Vol.288 (2), p.309-312
Main Authors: Høy, M, Chan, S L, Weng, X G, Gromada, J
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Clonidine - analogs & derivatives
Clonidine - pharmacology
Electrophysiology
Exocytosis - drug effects
Exocytosis - physiology
Female
Glucagon - secretion
In Vitro Techniques
Islets of Langerhans - drug effects
Islets of Langerhans - secretion
Membrane Proteins - physiology
Mice
Patch-Clamp Techniques
Potassium Channels
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Summary:Clonidine-displacing substance (CDS) is a potent stimulator of insulin release from pancreatic beta-cells and has been suggested to constitute the endogenous ligand for the islet imidazoline-binding site. Here we have explored the effects of CDS on glucagon release from mouse pancreatic alpha-cells. CDS (5 U/ml) produced a 35% inhibition (P < 0.05) of glucagon release from intact islets. This effect was dose-dependent and half-maximal inhibition by CDS was observed at 0.03 U/ml. Inhibition of glucagon release was not associated with a change in whole-cell ATP-sensitive K(+)-channel activity in single alpha-cells. However, during intracellular application through the recording pipette, CDS produced a 36% (P < 0.05) decrease in the rate of exocytosis, measured as changes in cell capacitance. The inhibitory effect of CDS on exocytosis resulted from activation of the protein phosphatase calcineurin and was abolished by cyclosporin A. These data provide further evidence for a role of CDS as an endogenous ligand controlling islet hormone secretion.
ISSN:0006-291X