| Literature DB >> 16581002 |
Julia Baumgartl1, Stephanie Baudler, Maximilian Scherner, Vladimir Babaev, Liza Makowski, Jill Suttles, Marcia McDuffie, Kazuyuki Tobe, Takashi Kadowaki, Sergio Fazio, C Ronald Kahn, Gökhan S Hotamisligil, Wilhelm Krone, Macrae Linton, Jens C Brüning.
Abstract
Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1beta expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2(-/-) ApoE(-/-) cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis.Entities:
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Year: 2006 PMID： 16581002 PMCID： PMC4027059 DOI： 10.1016/j.cmet.2006.02.010
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287