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

Sci Rep. 2017 Apr 10;7(1):779. doi: 10.1038/s41598-017-00900-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Biomarkers
  • Cell Line, Tumor
  • Exenatide
  • Gene Expression
  • Gene Targeting
  • Genetic Vectors / genetics
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Peptides / metabolism
  • Venoms / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Insulin
  • Peptides
  • SPHKAP protein, human
  • Venoms
  • Exenatide
  • Glucose