5 years ago

Serum quantitative proteomic analysis reveals soluble EGFR to be a marker of insulin resistance in male mice and humans.

Okuyama, Kyohara, Terauchi, Togashi, Shirakawa, Hirano, Tajima, Kimura
To identify circulating factors as candidates involved in type 2 diabetes (T2DM), we conducted two different quantitative proteomic analyses: 1) db/db mouse sera were compared with db/+ mouse sera obtained at 4, 8, 12, and 24 weeks of age, and 2) db/db mouse sera from animals treated with liraglutide were compared with sera from animals without liraglutide treatment. 20 and eight proteins were differentially expressed in db/db mouse sera in the first experiment and in db/db mouse sera after liraglutide treatment in the second experiment, respectively. Soluble epidermal growth factor receptor (sEGFR) was identified as a common factor, and its protein level was significantly affected in both experiments. An ELISA assay confirmed that the relatively low serum sEGFR levels in db/db mice were restored by liraglutide treatment. The serum sEGFR levels were elevated in diabetic mice with impaired insulin secretion and decreased in high-fat diet-fed mice and ob/ob mice. The serum sEGFR levels increased after the administration of a dual inhibitor of IGF-1/insulin receptor or streptozotocin. In humans with normal glucose tolerance or T2DM, the serum sEGFR levels were correlated with the fasting blood glucose, fasting serum insulin, HOMA-IR, HbA1c, total cholesterol, LDL-cholesterol, and triglycerides levels. These findings suggest that sEGFR might be a biomarker for evaluating insulin resistance or a therapeutic target of liraglutide.

Publisher URL: http://doi.org/10.1210/en.2017-00339

DOI: 10.1210/en.2017-00339

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