Sphingosine 1-phosphate stimulates insulin secretion in HIT-T 15 cells and mouse islets.
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.
Shimizu
H
H
The First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Okajima
F
F
Kimura
T
T
Ohtani
K
K
Tsuchiya
T
T
Takahashi
H
H
Kuwabara
A
A
Tomura
H
H
Sato
K
K
Mori
M
M
D016475:3T3 Cells; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008246:Lysophospholipids; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D004963:Estrenes; D007328:Insulin; D008246:Lysophospholipids; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343; C060506:sphingosine 1-phosphate; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D009543:Nifedipine; D013110:Sphingosine; D002118:Calcium