Sphingosine 1-phosphate stimulates insulin secretion in HIT-T 15 cells and mouse islets

Endocr J. 2000 Jun;47(3):261-9. doi: 10.1507/endocrj.47.261.


Sphingosine is involved in the regulation of cellular processes as a second messenger in various kinds of cells. Since the possible involvement of sphingosine has not been investigated in pancreatic beta-cells, we determined the expression of putative sphingosine 1-phosphate (S1P) receptors and the effect of sphingosine on pancreatic beta-cell function using a clonal Hamster beta-cell line, HIT-T 15 cells and isolated mouse islets. We showed the expression of putative S1P receptors, Edg-3 and AGR16/H218 in HIT-T 15 cells. Ten and 20 microM S1P significantly stimulated insulin secretion for 10 minutes in HIT-T 15 cells. Ten microM S1P significantly increased insulin secretion from isolated mouse islets. Ten microM S1P obviously increased intracellular Ca2+ concentration ([Ca2+]i). Fifty nM nifedipine did not affect the S1P stimulation of insulin secretion in HIT-T 15 cells. Two microM U73122 (phospholipase C inhibitor) completely deleted 10 microM S1P-induced stimulation of insulin secretion for 10 minutes, but U73343 (an inactive analogue of U73122) did not. S1P dose-dependently inhibited intracellular cyclic AMP levels. Pretreatment with 100 ng/ml pertussis toxin (PTX) partially, but significantly attenuated an increase of insulin secretion by 10 microM S1P. These data suggested that PTX-sensitive G-protein-dependent pathway may, at least in part, be involved in an increase of non-glucose stimulated insulin secretion by S1P through the activation of phospholipase C-Ca2+ system.

MeSH terms

  • 3T3 Cells
  • Adenylyl Cyclases / metabolism
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Cricetinae
  • Cyclic AMP / metabolism
  • Estrenes / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Lysophospholipids*
  • Mice
  • Nifedipine / pharmacology
  • Phosphodiesterase Inhibitors / pharmacology
  • Pyrrolidinones / pharmacology
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism


  • Estrenes
  • Insulin
  • Lysophospholipids
  • Phosphodiesterase Inhibitors
  • Pyrrolidinones
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • U 73343
  • sphingosine 1-phosphate
  • Cyclic AMP
  • Type C Phospholipases
  • Adenylyl Cyclases
  • Nifedipine
  • Sphingosine
  • Calcium