CD36 gene deletion reduces muscle insulin sensitivity in mice by up-regulating PTP1B expression.
10.12122/j.issn.1673-4254.2022.03.11
- Author:
Lin CHEN
1
;
Han ZENG
1
;
Hong QIN
1
;
Xiong Zhong RUAN
1
;
Ping YANG
1
Author Information
1. Chongqing Key Laboratory of Lipid and Glucose Metabolism, Center for Lipid Research, Chongqing Medical University, Chongqing 400016, China.
- Publication Type:Journal Article
- Keywords:
CD36;
PTP1B;
insulin sensitivity;
muscle
- MeSH:
Animals;
Gene Deletion;
Histones/genetics*;
Insulin;
Insulin Receptor Substrate Proteins/metabolism*;
Insulin Resistance/genetics*;
Membrane Cofactor Protein/genetics*;
Mice;
Mice, Knockout;
Muscles/metabolism*;
Phosphoric Monoester Hydrolases/metabolism*;
Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
RNA, Messenger/metabolism*;
Receptor, Insulin/metabolism*;
Tyrosine/genetics*;
Up-Regulation
- From:
Journal of Southern Medical University
2022;42(3):392-398
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect CD36 deficiency on muscle insulin signaling in mice fed a normal-fat diet and explore the possible mechanism.
METHODS:Wild-type (WT) mice and systemic CD36 knockout (CD36-/-) mice with normal feeding for 14 weeks (n=12) were subjected to insulin tolerance test (ITT) after intraperitoneal injection with insulin (1 U/kg). Real-time PCR was used to detect the mRNA expressions of insulin receptor (IR), insulin receptor substrate 1/2 (IRS1/2) and protein tyrosine phosphatase 1B (PTP1B), and Western blotting was performed to detect the protein expressions of AKT, IR, IRS1/2 and PTP1B in the muscle tissues of the mice. Tyrosine phosphorylation of IR and IRS1 and histone acetylation of PTP1B promoter in muscle tissues were detected using co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP), respectively.
RESULTS:CD36-/- mice showed significantly lowered insulin sensitivity with obviously decreased area under the insulin tolerance curve in comparison with the WT mice (P < 0.05). CD36-/- mice also had significantly higher serum insulin concentration and HOMA-IR than WT mice (P < 0.05). Western blotting showed that the p-AKT/AKT ratio in the muscle tissues was significantly decreased in CD36-/- mice as compared with the WT mice (P < 0.01). No significant differences were found in mRNA and protein levels of IR, IRS1 and IRS2 in the muscle tissues between WT and CD36-/- mice (P>0.05). In the muscle tissue of CD36-/- mice, tyrosine phosphorylation levels of IR and IRS1 were significantly decreased (P < 0.05), and the mRNA and protein levels of PTP1B (P < 0.05) and histone acetylation level of PTP1B promoters (P < 0.01) were significantly increased as compared with those in the WT mice. Intraperitoneal injection of claramine, a PTP1B inhibitor, effectively improved the impairment of insulin sensitivity in CD36-/- mice.
CONCLUSION:CD36 is essential for maintaining muscle insulin sensitivity under physiological conditions, and CD36 gene deletion in mice causes impaired insulin sensitivity by up-regulating muscle PTP1B expression, which results in detyrosine phosphorylation of IR and IRS1.
