Sphingosine 1-Phosphate Stimulates Insulin Secretion in HIT-T 15 Cells and Mouse Islets

[摘要] References(37)Cited-By(11)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 β-cells, we determined the expression of putative sphingosine 1-phosphate (S1P) receptors and the effect of sphingosine on pancreatic β-cell function using a clonal Hamster β-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 20μM S1P significantly stimulated insulin secretion for 10 minutes in HIT-T 15 cells. Ten μM S1P significantly increased insulin secretion from isolated mouse islets. Ten μM 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 μM U73122 (phospholipase C inhibitor) completely deleted 10μM 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 100ng/ml pertussis toxin (PTX) partially, but significantly attenuated an increase of insulin secretion by 10μM 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.

[学科分类] 内分泌与代谢学

[关键词] Sphingosine;Insulin;Ca2+;Phospholipase C;G-Protein