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

Life Sci. 2002 Jul 12;71(8):927-36. doi: 10.1016/s0024-3205(02)01774-5.


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.

MeSH terms

  • Amides / pharmacology
  • Animals
  • Arginine Vasopressin / pharmacology*
  • Calcium / metabolism*
  • Cell Line
  • Clone Cells
  • Cricetinae
  • Hormone Antagonists / pharmacology*
  • Indicators and Reagents
  • Indoles / pharmacology
  • Insulin / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Peptides, Cyclic / pharmacology
  • Receptors, Somatostatin / agonists
  • Receptors, Somatostatin / antagonists & inhibitors
  • Receptors, Somatostatin / physiology*
  • Somatostatin / pharmacology*


  • Amides
  • Hormone Antagonists
  • Indicators and Reagents
  • Indoles
  • Insulin
  • L 779976
  • PRL 2903
  • Peptides, Cyclic
  • Receptors, Somatostatin
  • Arginine Vasopressin
  • Somatostatin
  • somatostatin receptor 2
  • Calcium