Gliclazide directly inhibits arginine-induced glucagon release.
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 micro mol/l), which fully antagonizes the suppressive somatostatin effect on rat A cells. Gliclazide (30 micro mol/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.
Cejvan
Kenan
K
Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital and Institute, Stockholm, Sweden. kenan.cejvan@molmed.ki.se
Coy
David H
DH
Holst
Jens Juul
JJ
Cerasi
Erol
E
Efendic
Suad
S
D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005907:Gliclazide / Q000494:pharmacology*; D005934:Glucagon / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
C121568:PRL 2903; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D013453:Sulfonylurea Compounds; D013004:Somatostatin; D005934:Glucagon; D001120:Arginine; D005907:Gliclazide