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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Autores principales: Yu Wang, Shin-ichi Harashima, Yanyan Liu, Ryota Usui, Nobuya Inagaki
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/b1fa3fef52d4474db7a00a0becb7d055
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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
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