Somatostatin inhibits glucagon-like peptide-1-induced insulin secretion and proliferation of RINm5F insulinoma cells.
Glucagon-like peptide-1 [GLP-1; formerly GLP-1(7-36)amide] and somatostatin (SS) are two postprandially or paracrine released peptide hormones that regulate insulin secretion from pancreatic islets. Using the rat insulinoma cell line RINm5F as a model, we investigated the effects of both peptides alone and in combination on insulin release, proliferation, and intracellular signal transduction. In addition, we determined the SS receptor subtypes expressed and involved by reverse transcription-polymerase chain reaction and use of selective SS agonists. GLP-1 stimulated insulin release, cell proliferation, intracellular cAMP accumulation and activation of the transcription factor cAMP-response element binding protein (CREB) which all could be reduced to basal values by co-incubation with SS. Incubation with SS alone did not affect basal levels. RINm5F cells express the somatostatin receptor (sst) subtypes sst1 and sst2 as well as traces of sst3. In accordance, the sst1- or sst2-selective non-peptide agonists L-797591 or L-054522 and peptide agonist octreotide (SMS 201995; sst2, sst3, and sst5 selective) potently inhibited GLP-1-induced insulin secretion whereas the sst3-selective agonist L-796778 showed little effect. Moreover, the sst1- and sst2-selective agonists slightly reduced also basal insulin release. The experiments show that GLP-1 and SS are perfect opponents for regulating pancreatic beta-cell insulin secretion.
Stark
Alexander
A
Department of Anatomy, University of Kiel, Olshausenstrasse 40, D-24098, Kiel, Germany.
Mentlein
Rolf
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004347:Drug Interactions; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma; D010190:Pancreatic Neoplasms; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D014157:Transcription Factors; D013004:Somatostatin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP