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Sphingosine 1-phosphate Stimulates Insulin Secretion and Improves Cell Survival by Blocking Voltage-dependent K+ Channels in β Cells.

Authors :
Liu, Zhihong
Yang, Huanhuan
Zhi, Linping
Xue, Huan
Lu, Zhihong
Zhao, Yanli
Cui, Lijuan
Liu, Tao
Ren, Shouan
He, Peifeng
Liu, Yunfeng
Zhang, Yi
Source :
Frontiers in Pharmacology; 7/12/2021, Vol. 12, p1-13, 13p
Publication Year :
2021

Abstract

Recent studies suggest that Sphingosine 1-phosphate (S1P) plays an important role in regulating glucose metabolism in type 2 diabetes. However, its effects and mechanisms of promoting insulin secretion remain largely unknown. Here, we found that S1P treatment decreased blood glucose level and increased insulin secretion in C57BL/6 mice. Our results further showed that S1P promoted insulin secretion in a glucose-dependent manner. This stimulatory effect of S1P appeared to be irrelevant to cyclic adenosine monophosphate signaling. Voltage-clamp recordings showed that S1P did not influence voltage-dependent Ca<superscript>2+</superscript> channels, but significantly blocked voltage-dependent potassium (Kv) channels, which could be reversed by inhibition of phospholipase C (PLC) and protein kinase C (PKC). Calcium imaging revealed that S1P increased intracellular Ca<superscript>2+</superscript> levels, mainly by promoting Ca<superscript>2+</superscript> influx, rather than mobilizing intracellular Ca<superscript>2+</superscript> stores. In addition, inhibition of PLC and PKC suppressed S1P-induced insulin secretion. Collectively, these results suggest that the effects of S1P on glucose-stimulated insulin secretion (GSIS) depend on the inhibition of Kv channels via the PLC/PKC signaling pathway in pancreatic β cells. Further, S1P improved β cell survival; this effect was also associated with Kv channel inhibition. This work thus provides new insights into the mechanisms whereby S1P regulates β cell function in diabetes. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16639812
Volume :
12
Database :
Complementary Index
Journal :
Frontiers in Pharmacology
Publication Type :
Academic Journal
Accession number :
151401629
Full Text :
https://doi.org/10.3389/fphar.2021.683674