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MCPIP‐1 deficiency induces hepatic inflammation and impairs insulin signaling in mice
Author(s) -
CHANG YINGZI,
Holdaway Brett Benson,
Moody Joshua Dan,
Fu Mingui,
Kolattukudy Pappachan
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.918.5
Subject(s) - inflammation , insulin receptor , insulin tolerance test , medicine , insulin , endocrinology , immune system , insulin receptor substrate , monocyte , signal transduction , protein kinase b , insulin resistance , irs1 , diabetes mellitus , biology , immunology , microbiology and biotechnology , insulin sensitivity
Emerging evidence suggests that elevated inflammatory/immune events are associated with pathogenesis of diabetes. MCPIP1 (monocyte chemotactic protein [MCP]–induced protein 1; also known as ZC3H12A ), an immune response modifier expressed in mice macrophage in response to LPS and MCP‐1 stimulation, plays a negative role in the process of inflammation. Our current study was designed to test if MCPIP‐1 deficiency induced metabolic dysfunction by affecting the insulin signaling transduction pathway. Wild‐type C57/BL6 mice and MCPIP‐1 knockout mice with the C57/BL6 background were used. We found that MCPIP‐1‐deficient mice showed severe hepatic inflammation and remodeling, lower fasting plasma insulin levels (p<0.05), delayed response to the glucose challenge (p<0.05), and reduced insulin tolerance (p<0.05). Our results also revealed that insulin‐induced phosphorylation of insulin receptor (IR), insulin receptor substrate 1(IRS‐1), and AKT were substantially decreased in the liver from MCPIP1‐deficient mice. In conclusion, MCPIP‐1 deficiency impairs insulin production, insulin signaling transduction, and the ability of enduring metabolic challenges by inducing hepatic inflammation. Funded by Warner's grant, A.T. Still University of Health Sciences.