PMID- 29028997 OWN - NLM STAT- MEDLINE DCOM- 20171218 LR - 20181202 IS - 1945-7170 (Electronic) IS - 0013-7227 (Linking) VI - 158 IP - 12 DP - 2017 Dec 1 TI - Serum Quantitative Proteomic Analysis Reveals Soluble EGFR To Be a Marker of Insulin Resistance in Male Mice and Humans. PG - 4152-4164 LID - 10.1210/en.2017-00339 [doi] AB - To identify circulating factors as candidates involved in type 2 diabetes mellitus (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. Twenty proteins were differentially expressed in db/db mouse sera in the first experiment and eight proteins were differentially expressed in db/db mouse sera after liraglutide treatment in the second experiment. Soluble epidermal growth factor receptor (sEGFR) was identified as a common factor, and its protein level was significantly affected in both experiments. An enzyme-linked immunosorbent 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, homeostatic model assessment of insulin resistance, HbA1c, total cholesterol, low-density lipoprotein cholesterol, and triglycerides levels. These findings suggest that sEGFR might be a biomarker for evaluating insulin resistance or a therapeutic target of liraglutide. CI - Copyright (c) 2017 Endocrine Society. FAU - Kyohara, Mayu AU - Kyohara M AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Japan. FAU - Shirakawa, Jun AU - Shirakawa J AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Japan. FAU - Okuyama, Tomoko AU - Okuyama T AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Japan. FAU - Kimura, Ayuko AU - Kimura A AD - Advanced Medical Research Center, Yokohama City University, Japan. FAU - Togashi, Yu AU - Togashi Y AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Japan. FAU - Tajima, Kazuki AU - Tajima K AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Japan. FAU - Hirano, Hisashi AU - Hirano H AD - Advanced Medical Research Center, Yokohama City University, Japan. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Japan. LA - eng SI - UMIN CTR/UMIN000020474 PT - Journal Article PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Lipids) RN - 0 (Proteome) RN - 839I73S42A (Liraglutide) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Animals MH - Biomarkers/*blood MH - Blood Glucose/metabolism MH - Diabetes Mellitus, Type 2/blood/drug therapy MH - Enzyme-Linked Immunosorbent Assay MH - ErbB Receptors/antagonists & inhibitors/*blood MH - Humans MH - Hypoglycemic Agents/pharmacology MH - Insulin/blood MH - *Insulin Resistance MH - Lipids/blood MH - Liraglutide/pharmacology MH - Male MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Proteome/*metabolism MH - Proteomics/*methods EDAT- 2017/10/14 06:00 MHDA- 2017/12/19 06:00 CRDT- 2017/10/14 06:00 PHST- 2017/04/07 00:00 [received] PHST- 2017/09/29 00:00 [accepted] PHST- 2017/10/14 06:00 [pubmed] PHST- 2017/12/19 06:00 [medline] PHST- 2017/10/14 06:00 [entrez] AID - 4344850 [pii] AID - 10.1210/en.2017-00339 [doi] PST - ppublish SO - Endocrinology. 2017 Dec 1;158(12):4152-4164. doi: 10.1210/en.2017-00339.