| First Author | Alliouachene S | Year | 2015 |
| Journal | Cell Rep | Volume | 13 |
| Issue | 9 | Pages | 1881-94 |
| PubMed ID | 26655903 | Mgi Jnum | J:252034 |
| Mgi Id | MGI:6102145 | Doi | 10.1016/j.celrep.2015.10.052 |
| Citation | Alliouachene S, et al. (2015) Inactivation of the Class II PI3K-C2beta Potentiates Insulin Signaling and Sensitivity. Cell Rep 13(9):1881-94 |
| abstractText | In contrast to the class I phosphoinositide 3-kinases (PI3Ks), the organismal roles of the kinase activity of the class II PI3Ks are less clear. Here, we report that class II PI3K-C2beta kinase-dead mice are viable and healthy but display an unanticipated enhanced insulin sensitivity and glucose tolerance, as well as protection against high-fat-diet-induced liver steatosis. Despite having a broad tissue distribution, systemic PI3K-C2beta inhibition selectively enhances insulin signaling only in metabolic tissues. In a primary hepatocyte model, basal PI3P lipid levels are reduced by 60% upon PI3K-C2beta inhibition. This results in an expansion of the very early APPL1-positive endosomal compartment and altered insulin receptor trafficking, correlating with an amplification of insulin-induced, class I PI3K-dependent Akt signaling, without impacting MAPK activity. These data reveal PI3K-C2beta as a critical regulator of endosomal trafficking, specifically in insulin signaling, and identify PI3K-C2beta as a potential drug target for insulin sensitization. |
