IRS-2 deficiency in macrophages promotes their accumulation in the vascular wall

The aim of this study was to investigate the role of insulin receptor substrate-2 (IRS-2) mediated signal in macrophages on the accumulation of macrophages in the vascular wall. Mice transplanted with IRS-2−/− bone marrow, a model of myeloid cell restricted defect of IRS-2, showed accumulation of monocyte chemoattractant protein-1-expressing macrophages in the vascular wall. Experiments using cultured peritoneal macrophages showed that IRS-2-mediated signal pathway stimulated by physiological concentrations of insulin, not by IL-4, contributed to the suppression of monocyte chemoattractant protein-1 expression induced by lipopolysaccharide. Our data indicated that IRS-2 deficiency in macrophages enhanced their accumulation in the vascular wall accompanied by increased expression of proinflammatory mediators in macrophages. These results suggest a role for insulin resistance in macrophages in early atherosclerogenesis.

► Myeloid cell restricted IRS-2 KO mice were used in this study.
► These mice show accumulation of macrophages in vascular wall.
► The macrophages highly express MCP-1.
► Insulin suppressed MCP-1 expression in cultured macrophages.
► IRS-2 is essential for this reaction.