Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion
Abstract Glucose-stimulated insulin secretion (GSIS) is essential in keeping blood glucose levels within normal range. GSIS is impaired in type 2 diabetes, and its recovery is crucial in treatment of the disease. We find here that sphingosine kinase 1-interacting protein (SKIP, also called Sphkap) i...
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Nature Portfolio
2017
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oai:doaj.org-article:b1fa3fef52d4474db7a00a0becb7d0552021-12-02T16:06:01ZSphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion10.1038/s41598-017-00900-72045-2322https://doaj.org/article/b1fa3fef52d4474db7a00a0becb7d0552017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00900-7https://doaj.org/toc/2045-2322Abstract Glucose-stimulated insulin secretion (GSIS) is essential in keeping blood glucose levels within normal range. GSIS is impaired in type 2 diabetes, and its recovery is crucial in treatment of the disease. We find here that sphingosine kinase 1-interacting protein (SKIP, also called Sphkap) is highly expressed in pancreatic β-cells but not in α-cells. Intraperitoneal glucose tolerance test showed that plasma glucose levels were decreased and insulin levels were increased in SKIP−/− mice compared to SKIP+/+ mice, but exendin-4-enhanced insulin secretion was masked. GSIS was amplified more in SKIP−/− but exendin-4-enhanced insulin secretion was masked compared to that in SKIP+/+ islets. The ATP and cAMP content were similarly increased in SKIP+/+ and SKIP−/− islets; depolarization-evoked, PKA and cAMP-mediated insulin secretion were not affected. Inhibition of PDE activity equally augmented GSIS in SKIP+/+ and SKIP−/− islets. These results indicate that SKIP modulates GSIS by a pathway distinct from that of cAMP-, PDE- and sphingosine kinase-dependent pathways.Yu WangShin-ichi HarashimaYanyan LiuRyota UsuiNobuya InagakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q Yu Wang Shin-ichi Harashima Yanyan Liu Ryota Usui Nobuya Inagaki Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion |
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Abstract Glucose-stimulated insulin secretion (GSIS) is essential in keeping blood glucose levels within normal range. GSIS is impaired in type 2 diabetes, and its recovery is crucial in treatment of the disease. We find here that sphingosine kinase 1-interacting protein (SKIP, also called Sphkap) is highly expressed in pancreatic β-cells but not in α-cells. Intraperitoneal glucose tolerance test showed that plasma glucose levels were decreased and insulin levels were increased in SKIP−/− mice compared to SKIP+/+ mice, but exendin-4-enhanced insulin secretion was masked. GSIS was amplified more in SKIP−/− but exendin-4-enhanced insulin secretion was masked compared to that in SKIP+/+ islets. The ATP and cAMP content were similarly increased in SKIP+/+ and SKIP−/− islets; depolarization-evoked, PKA and cAMP-mediated insulin secretion were not affected. Inhibition of PDE activity equally augmented GSIS in SKIP+/+ and SKIP−/− islets. These results indicate that SKIP modulates GSIS by a pathway distinct from that of cAMP-, PDE- and sphingosine kinase-dependent pathways. |
format |
article |
author |
Yu Wang Shin-ichi Harashima Yanyan Liu Ryota Usui Nobuya Inagaki |
author_facet |
Yu Wang Shin-ichi Harashima Yanyan Liu Ryota Usui Nobuya Inagaki |
author_sort |
Yu Wang |
title |
Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion |
title_short |
Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion |
title_full |
Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion |
title_fullStr |
Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion |
title_full_unstemmed |
Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion |
title_sort |
sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/b1fa3fef52d4474db7a00a0becb7d055 |
work_keys_str_mv |
AT yuwang sphingosinekinase1interactingproteinisanovelregulatorofglucosestimulatedinsulinsecretion AT shinichiharashima sphingosinekinase1interactingproteinisanovelregulatorofglucosestimulatedinsulinsecretion AT yanyanliu sphingosinekinase1interactingproteinisanovelregulatorofglucosestimulatedinsulinsecretion AT ryotausui sphingosinekinase1interactingproteinisanovelregulatorofglucosestimulatedinsulinsecretion AT nobuyainagaki sphingosinekinase1interactingproteinisanovelregulatorofglucosestimulatedinsulinsecretion |
_version_ |
1718385169554997248 |