C-reactive protein causes insulin resistance in mice through fcg receptor IIB-mediated inhibition of skeletal muscle glucose delivery

Keiji Tanigaki, Wanpen Vongpatanasin, Jose A. Barrera, Dmitriy N. Atochin, Paul L. Huang, Ezio Bonvini, Philip W. Shaul, Chieko Mineo

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Elevations in C-reactive protein (CRP) are associated with an increased risk of insulin resistance. Whether CRP plays a causal role is unknown. Here we show that CRP transgenic mice and wild-type mice administered recombinant CRP are insulin resistant. Mice lacking the inhibitory Fcg receptor IIB (FcgRIIB) are protected from CRP-induced insulin resistance, and immunohistochemistry reveals that FcgRIIB is expressed in skeletal muscle microvascular endothelium and is absent in skeletal muscle myocytes, adipocytes, and hepatocytes. The primary mechanism in glucose homeostasis disrupted by CRP is skeletal muscle glucose delivery, and CRP attenuates insulin-induced skeletal muscle blood flow. CRP does not impair skeletal muscle glucose delivery in FcgRIIB2/2 mice or in endothelial nitric oxide synthase knock-in mice with phosphomimetic modification of Ser1176, which is normally phosphorylated by insulin signaling to stimulate nitric oxide-mediated skeletal muscle blood flow and glucose delivery and is dephosphorylated by CRP/FcgRIIB. Thus, CRP causes insulin resistance in mice through FcgRIIBmediated inhibition of skeletal muscle glucose delivery.

Original languageEnglish
Pages (from-to)721-731
Number of pages11
JournalDiabetes
Volume62
Issue number3
DOIs
Publication statusPublished - Mar 2013
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Tanigaki, K., Vongpatanasin, W., Barrera, J. A., Atochin, D. N., Huang, P. L., Bonvini, E., Shaul, P. W., & Mineo, C. (2013). C-reactive protein causes insulin resistance in mice through fcg receptor IIB-mediated inhibition of skeletal muscle glucose delivery. Diabetes, 62(3), 721-731. https://doi.org/10.2337/db12-0133