Effects and possible mechanism of sphingosine-1-phosphate-stimulated insulin secretion from rat islets / 中国药理学通报

ABSTRACT

Aim To observe the effects of glucose-stim-ulated insulin secretion ( GSIS ) on rat islets after S1 P treatments and the underlying molecular mechanisms. Methods Collagenase P and Histopaque 1077 were used to digest and isolate rat pancreatic islets, and Dispase II was used to digest pancreatic islet to obtain pancreatic cells. Insulin secretions were measured after S1P (0~20 μmol·L-1 ) treatment under low glucose ( LG, 2. 8 mmol·L-1 ) and high glucose ( HG, 16. 7 mmol·L-1 ) conditions. Patch-clamp recordings were applied to monitor voltage-dependent potassium chan-nel currents (Kv currents) after S1P treatment. Calci-um image technique was used to measure the changes of intracellular Ca2+ concentration after S1P ( 0 ~20μmol·L-1 ) treatments. Results HG group signifi-cantly increased insulin secretion compared to LG group ( P0. 05 ) . S1 P increased insulin secretion significantly in a dose-dependent man-ner under HG condition ( P<0. 01 ) . Kv currents ofβcells were inhibited significantly after S1 P treatment ( P<0. 01 ) . S1 P increased the concentrations of in-tracellular Ca2+ in a dose-dependent manner under HG condition( P <0. 01) . Conclusion S1P may pro-mote GSIS by inhibiting Kv currents and increasing the level of intracellular Ca2+.