Intra-islet somatostatin regulates glucagon release via type 2 somatostatin receptors in rats.
Exogenously administered somatostatin (SST) inhibits secretion of insulin and glucagon. Furthermore, it is hypothesized that islet SST regulates glucagon secretion by a local action. A number of studies utilizing SST antibodies have been performed to test this hypothesis, and their results have been conflicting. Five subtypes of SST receptor (SSTR1-5) mediate the effect of SST on target cells. In rodents, SST inhibits the release of glucagon, but not that of insulin, via SSTR2. A novel SSTR2-selective antagonist, DC-41-33, was synthesized recently. We have investigated the effects of this antagonist on arginine-stimulated glucagon and insulin release in batch incubations of isolated rat islets, perifused isolated rat islets, and isolated perfused rat pancreas. In batch incubations at 3.3 mmol/l glucose, DC-41-33 increased glucagon release in a dose-dependent manner. At the maximum dose tested (2 micro mol/l), DC-41-33 enhanced the glucagon response by 4.3- to 5-fold. Similarly, this compound increased arginine-induced glucagon release in perifused islets at 3.3 mmol/l glucose (2.8-fold) and perfused pancreas at 3.3 and 5.5 mmol/l glucose (2.5- and 2.3-fold, respectively). In the two latter experimental systems, DC-41-33 had no significant effect on insulin release. In conclusion, our results strongly support the hypothesis that islet SST inhibits glucagon secretion via a local action.
Cejvan
Kenan
K
Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital and Institute, L6:02, S-171 76 Stockholm, Sweden. kenen.cejvan@molmed.ki.se
Coy
David H
DH
Efendic
Suad
S
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D005786:Gene Expression Regulation; D005934:Glucagon / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics*; D013004:Somatostatin / Q000494:pharmacology / Q000502:physiology*
D007328:Insulin; C121568:PRL 2903; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D013004:Somatostatin; D005934:Glucagon; D001120:Arginine; C093733:somatostatin receptor 2