Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
Sci Rep. 2017 Apr 10;7(1):779. doi: 10.1038/s41598-017-00900-7.
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.
葡萄糖刺激的胰岛素分泌（GSIS）对于维持血糖水平在正常范围内至关重要。2 型糖尿病患者的 GSIS 受损，其恢复对于治疗该疾病至关重要。我们在这里发现，鞘氨醇激酶 1 相互作用蛋白（SKIP，也称为 Sphkap）在胰岛β细胞中高度表达，但在胰岛α细胞中不表达。腹腔葡萄糖耐量试验显示，与 SKIP 小鼠相比，SKIP 小鼠的血浆葡萄糖水平降低，胰岛素水平升高，但外泌素-4 增强的胰岛素分泌被掩盖。与 SKIP 胰岛相比，SKIP 中的 GSIS 被放大更多，但外泌素-4 增强的胰岛素分泌被掩盖。在 SKIP 和 SKIP 胰岛中，ATP 和 cAMP 含量同样增加；去极化诱发的、PKA 和 cAMP 介导的胰岛素分泌不受影响。PDE 活性的抑制同样增强了 SKIP 和 SKIP 胰岛中的 GSIS。这些结果表明，SKIP 通过不同于 cAMP、PDE 和鞘氨醇激酶依赖性途径的途径来调节 GSIS。
