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

26 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

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C-Reactive Protein
Insulin Resistance
Skeletal Muscle
Glucose
Insulin
Nitric Oxide Synthase Type III
Skeletal Muscle Fibers
Recombinant Proteins
Adipocytes
Transgenic Mice
Endothelium
Blood Glucose
Hepatocytes
Nitric Oxide
Homeostasis
Immunohistochemistry

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

C-reactive protein causes insulin resistance in mice through fcg receptor IIB-mediated inhibition of skeletal muscle glucose delivery. / Tanigaki, Keiji; Vongpatanasin, Wanpen; Barrera, Jose A.; Atochin, Dmitriy N.; Huang, Paul L.; Bonvini, Ezio; Shaul, Philip W.; Mineo, Chieko.

In: Diabetes, Vol. 62, No. 3, 03.2013, p. 721-731.

Research output: Contribution to journalArticle

Tanigaki, K, Vongpatanasin, W, Barrera, JA, Atochin, DN, Huang, PL, Bonvini, E, Shaul, PW & Mineo, C 2013, 'C-reactive protein causes insulin resistance in mice through fcg receptor IIB-mediated inhibition of skeletal muscle glucose delivery', Diabetes, vol. 62, no. 3, pp. 721-731. https://doi.org/10.2337/db12-0133
Tanigaki, Keiji ; Vongpatanasin, Wanpen ; Barrera, Jose A. ; Atochin, Dmitriy N. ; Huang, Paul L. ; Bonvini, Ezio ; Shaul, Philip W. ; Mineo, Chieko. / C-reactive protein causes insulin resistance in mice through fcg receptor IIB-mediated inhibition of skeletal muscle glucose delivery. In: Diabetes. 2013 ; Vol. 62, No. 3. pp. 721-731.
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