Gliclazide Directly Inhibits Arginine-Induced Glucagon Release
- 1Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital and Institute, Stockholm, Sweden
- 2Peptide Research Laboratories, Department of Medicine, Tulane Health Sciences Center, New Orleans, Louisiana
- 3Department of Medical Physiology, University of Copenhagen, Panum Institute, Copenhagen, Denmark
- 4Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel
Abstract
Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of gliclazide or was secondary to the paracrine effect of released somatostatin. To eliminate the paracrine effects of somatostatin, we first perfused isolated rat pancreata with a medium supplemented with 23% of the standard calcium content. Second, we perifused isolated rat islets with a novel and highly specific antagonist of type 2 somatostatin receptor, DC-41-33 (2 μmol/l), which fully antagonizes the suppressive somatostatin effect on rat A cells. Gliclazide (30 μmol/l) inhibited glucagon release by 54% in the perfusion experiments, whereas the somatostatin response was nearly abolished. In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell.
Footnotes
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Address correspondence and reprint requests to Kenan Cejvan, Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden. E-mail: kenan.cejvan{at}molmed.ki.se.
Received for publication 19 March 2002 and accepted in revised form 16 May 2002.
AUC, area under the curve; KRBB, Krebs-Ringer bicarbonate buffer; SSTR, somatostatin receptor; STZ, streptozotocin; KATP channel, ATP-sensitive potassium channel.
The symposium and the publication of this article have been made possible by an unrestricted educational grant from Servier, Paris.
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