| First Author | Liu Y | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 5 | Pages | 6239-6253 |
| PubMed ID | 30789757 | Mgi Jnum | J:291975 |
| Mgi Id | MGI:6447426 | Doi | 10.1096/fj.201801783RR |
| Citation | Liu Y, et al. (2019) Sphingosine kinase 1-interacting protein is a dual regulator of insulin and incretin secretion. FASEB J 33(5):6239-6253 |
| abstractText | Our previous study demonstrated that sphingosine kinase 1-interacting protein (SKIP, or Sphkap) is expressed in pancreatic beta-cells, and depletion of SKIP enhances glucose-stimulated insulin secretion. We find here that SKIP is also expressed in intestinal K- and L-cells and that secretion of gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) as well as insulin are significantly increased, and blood glucose levels are decreased in SKIP-deficient (SKIP(-/-)) mice compared with those in wild-type mice. Plasma triglyceride (Tg), LDL cholesterol, and mRNA levels of proinflammatory cytokines in adipose tissues, livers, and intestines were found to be significantly decreased in SKIP(-/-) mice. The phenotypic characteristics of SKIP(-/-) mice, including adiposity and attenuation of basal inflammation, were abolished by genetic depletion of GIP. The improvement of glucose tolerance and lipid profiles in SKIP(-/-) mice were cancelled by GLP-1 receptor antagonist exendin-(9-39) treatment. In summary, depletion of SKIP ameliorates glucose tolerance by enhancing secretion of insulin and incretins, improves lipid metabolism, and reduces basal inflammation levels. Thus, inhibition of SKIP action may emerge as a new option for treatment of type 2 diabetes mellitus with metabolic dysfunction.-Liu, Y., Harashima, S., Wang, Y., Suzuki, K., Tokumoto, S., Usui, R., Tatsuoka, H., Tanaka, D., Yabe, D., Harada, N., Hayashi, Y., Inagaki, N. Sphingosine kinase 1-interacting protein is a dual regulator of insulin and incretin secretion. |
