Enhanced PIP3 signaling in POMC neurons causes diet-sensitive obesity as the consequence of neuronal silencing via KATP channel activation
L Plum, X Ma, B Hampel, H Münzberg, M Shanabrough, E Rother, L Koch, R Janoschek, J Alber, BF Belgardt, W Krone, TL Horvath, FM Ashcroft, JC Brüning · Diabetologie und Stoffwechsel · 2006 · Heft 06
Bibliografische Angaben
Zusammenfassung
Leptin and insulin have been identified as fuel sensors acting in part through their hypothalamic receptors to inhibit food intake and stimulate energy expenditure. Both insulin and leptin receptors efficiently activate insulin receptor substrate-dependent signaling leading to activation of the phosphatidyl-inositol (PI) 3-kinase and subsequent generation of PI3,4,5-trisphosphate (PIP3). We directly addressed the role of PIP3-mediated signals in hypothalamic proopiomelanocortin (POMC) neurons by inactivating the gene for the PIP3 phosphatase Pten specifically in this cell type. Here we show that POMC-specific di…
