title: 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 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.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan. harasima@kuhp.kyoto-u.ac.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Harashima
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Usui
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan. inagaki@kuhp.kyoto-u.ac.jp.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D045744:Cell Line, Tumor; D000077270:Exenatide; D015870:Gene Expression; D018390:Gene Targeting; D005822:Genetic Vectors / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010455:Peptides / Q000378:metabolism; D014688:Venoms / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D007328:Insulin; D010455:Peptides; C466999:SPHKAP protein, human; D014688:Venoms; D000077270:Exenatide; D005947:Glucose