| First Author | Song EK | Year | 2012 |
| Journal | Cell Rep | Volume | 2 |
| Issue | 6 | Pages | 1607-19 |
| PubMed ID | 23177620 | Mgi Jnum | J:324781 |
| Mgi Id | MGI:6852261 | Doi | 10.1016/j.celrep.2012.10.018 |
| Citation | Song EK, et al. (2012) NAADP mediates insulin-stimulated glucose uptake and insulin sensitization by PPARgamma in adipocytes. Cell Rep 2(6):1607-19 |
| abstractText | Insulin stimulates glucose uptake through the membrane translocation of GLUT4 and GLUT1. Peroxisome proliferator-activated receptor gamma (PPARgamma) enhances insulin sensitivity. Here, we demonstrate that insulin stimulates GLUT4 and GLUT1 translocation, and glucose uptake, by activating the signaling pathway involving nicotinic acid adenine dinucleotide phosphate (NAADP), a calcium mobilizer, in adipocytes. We also demonstrate that PPARgamma mediates insulin sensitization by enhancing NAADP production through upregulation of CD38, the only enzyme identified for NAADP synthesis. Insulin produced NAADP by both CD38-dependent and -independent pathways, whereas PPARgamma produced NAADP by CD38-dependent pathway. Blocking the NAADP signaling pathway abrogated both insulin-stimulated and PPARgamma-induced GLUT4 and GLUT1 translocation, thereby inhibiting glucose uptake. CD38 knockout partially inhibited insulin-stimulated glucose uptake. However, CD38 knockout completely blocked PPARgamma-induced glucose uptake in adipocytes and PPARgamma-mediated amelioration of glucose tolerance in diabetic mice. These results demonstrated that the NAADP signaling pathway is a critical molecular target for PPARgamma-mediated insulin sensitization. |
