| First Author | Kobayashi N | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 14 | Pages | 5753-8 |
| PubMed ID | 21436039 | Mgi Jnum | J:171214 |
| Mgi Id | MGI:4949003 | Doi | 10.1073/pnas.1016430108 |
| Citation | Kobayashi N, et al. (2011) Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance. Proc Natl Acad Sci U S A 108(14):5753-8 |
| abstractText | Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kgamma) in inflammatory states, little is known about the role of PI3Kgamma in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kgamma in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110gamma (Pik3cg(-/-)), the catalytic subunit of PI3Kgamma, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg(-/-) mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kgamma also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kgamma plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kgamma can be a therapeutic target for type 2 diabetes. |
