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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) is highly expressed in pancreatic ?-cells but not in ?-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.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC5429731 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion.

Wang Yu Y   Harashima Shin-Ichi SI   Liu Yanyan Y   Usui Ryota R   Inagaki Nobuya N  

Scientific reports 20170410 1


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<sup>-/-</sup> mice  ...[more]

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