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Loss of CD36 impairs hepatic insulin signaling by enhancing the interaction of PTP1B with IR

Yang, P; Zeng, H; Tan, W; Luo, X; Zheng, E; Zhao, L; Wei, L; ... Chen, Y; + view all (2020) Loss of CD36 impairs hepatic insulin signaling by enhancing the interaction of PTP1B with IR. FASEB Journal , 34 (4) pp. 5658-5672. 10.1096/fj.201902777RR. Green open access

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Abstract

A contradictory role of CD36 in insulin resistance was found to be related to the nutrient state. Here, we examined that the physiological functions of CD36 in insulin signal transduction in mice fed a low‐fat diet. CD36 deficiency led to hepatic insulin resistance and decreased insulin‐stimulated tyrosine phosphorylation of insulin receptor β (IRβ) in mice fed a low‐fat diet. The ability of insulin to bind with IR did not differ between WT and CD36‐deficient hepatocytes. CD36 formed a complex with IRβ and dissociation of CD36/Fyn complex or inhibition of Fyn only partially reversed the effects of CD36 on hepatic insulin signaling. Furthermore, we found that CD36 deficiency led to abnormally increased hepatic protein‐tyrosine phosphatase 1B (PTP1B) expression and enhanced PTP1B and IR interactions, which contributed to the decreased insulin signaling and disordered glucose metabolism. In addition, increased endoplasmic reticulum (ER) stress was found in the livers of the CD36‐deficient mice, while inhibited ER stress normalized the PTP1B expression and restored insulin signaling in the CD36‐deficient mice. Our findings suggest that the loss of CD36 impairs hepatic insulin signaling by enhancing the PTP1B/IR interaction that is induced by ER stress, indicating a possible critical step in the progression of hepatic insulin resistance.

Type: Article
Title: Loss of CD36 impairs hepatic insulin signaling by enhancing the interaction of PTP1B with IR
Open access status: An open access version is available from UCL Discovery
DOI: 10.1096/fj.201902777RR
Publisher version: https://doi.org/10.1096/fj.201902777RR
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions
Keywords: CD36, ER stress, insulin sensitivity, IR, PTP1B
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10099718
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