Format

Send to

Choose Destination
Cell Metab. 2006 Apr;3(4):247-56.

Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis.

Author information

1
Institute for Genetics, University of Cologne and Center of Molecular Medicine Cologne, D-50931 Cologne, Germany.

Erratum in

  • Cell Metab. 2006 Jun;3(6):469. Tobe, Kazuyuki [added]; Kadowaki, Takashi [added].

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.

PMID:
16581002
PMCID:
PMC4027059
DOI:
10.1016/j.cmet.2006.02.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center