SSTR2 mediates the somatostatin-induced increase in intracellular Ca(2+) concentration and insulin secretion in the presence of arginine vasopressin in clonal beta-cell HIT-T15.
The effects of somatostatin (SRIF) are mediated through the seven transmembrane receptor family that signals via Gi/Go. To date, five distinct SRIF receptors have been characterized and designated SSTR1-5. We have characterized the SRIF receptor that mediates the increase in [Ca(2+)](i) and insulin secretion in HIT-T15 cells (Simian virus 40-transformed Syrian hamster islets) using high affinity, subtype selective agonists for SSTR1 (L-797,591), SSTR2 (L-779,976), SSTR3 (L-796,778), SSTR4 (L-803,087), SSTR5 (L-817,818) and PRL-2903, a specific SSTR2 antagonist. In the presence of arginine vasopressin (AVP), SRIF increased [Ca(2+)](i) and insulin secretion. Treatment with the SSTR2 agonist L-779,976 resulted in similar responses to SRIF. In addition, L-779,976 increased both [Ca(2+)](i) and insulin secretion in a dose-dependent manner. Treatment with L-779,976 alone did not alter [Ca(2+)](i) or basal insulin secretion. In the presence of AVP, all other SRIF receptor agonists failed to increase [Ca(2+)](i) and insulin secretion. The effects of SRIF and L-779,976 were abolished by the SSTR2 antagonist PRL-2903. Our results suggest that the mechanism underlying SRIF-induced insulin secretion in HIT-T15 cells be mediated through the SSTR2.
Cheng
Henrique
H
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011 USA.
Yibchok-anun
Sirintorn
S
Coy
David H
DH
Hsu
Walter H
WH
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D006224:Cricetinae; D006727:Hormone Antagonists / Q000494:pharmacology*; D007202:Indicators and Reagents; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology*
D000577:Amides; D006727:Hormone Antagonists; D007202:Indicators and Reagents; D007211:Indoles; D007328:Insulin; C121854:L 779976; C121568:PRL 2903; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D001127:Arginine Vasopressin; D013004:Somatostatin; C093733:somatostatin receptor 2; D002118:Calcium