title: Fatty Liver and Insulin Resistance in the Liver-Specific Knockout Mice of Mitogen Inducible Gene-6.
abstract: Mitogen inducible gene-6 (Mig-6) is a feedback inhibitor of epidermal growth factor receptor (EGFR) signaling pathway. The liver-specific knockout mice of the Mig-6 gene (Mig-6d/d) showed hepatomegaly and increased hypercholesterolemia. In this study, the biomarkers of insulin resistance and the effects of high-fat diets in the wild (Mig-6f/f) and Mig-6d/dmice were analyzed. The fasting plasma concentrations of glucose, triglyceride, cholesterols, free fatty acids, and HOMA-IR were measured and the glucose tolerance and insulin resistance tests were performed in the 25-week-old Mig-6f/fand the Mig-6d/dmice. The protein levels of active insulin receptor, glucose 6-phosphatase, and phosphoenolpyruvate carboxykinase were analyzed in the liver and fat. The fasting plasma cholesterol and glucose concentration were higher in the Mig-6d/dmice than the Mig-6f/fmice with increased fat deposition in the liver. But the Mig-6d/dmice had the improved glucose intolerance and insulin resistance without increased amount of phosphoinsulin receptor after insulin infusion in the liver. The hepatic concentration of phosphoenolpyruvate carboxykinase was increased in fasting Mig-6d/dmice. The feeding of high-fat diet accelerated the plasma lipids profiles and HOMA-IR in the Mig-6d/dmice but had no differential effects in oral glucose tolerance test and insulin tolerance test in both genotypes. These results suggest that the activated EGFR signaling might increase the fasting plasma glucose concentration through inducing the hepatic steatosis and the improved whole-body insulin resistance in the KO mice be caused by decreased adipogenesis in fat tissues.
authors.affiliation: Research Center for Drug Discovery Technology, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea; Department of Drug Development and Discovery, Graduate School of New Drug Development and Discovery, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Byung Kil
authors.initials: BK
authors.lastname: Park
authors.affiliation: Research Center for Drug Discovery Technology, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea; Department of Drug Development and Discovery, Graduate School of New Drug Development and Discovery, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Eun-Ah
authors.identifier: 0000-0001-7739-5977
authors.initials: EA
authors.lastname: Lee
authors.affiliation: Research Center for Drug Discovery Technology, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Hee-Youn
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Jun Choul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Koon Soon
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Research Center for Drug Discovery Technology, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Won Hoon
authors.initials: WH
authors.lastname: Jeong
authors.affiliation: Research Center for Drug Discovery Technology, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Bon Jeong
authors.identifier: 0000-0002-3414-8949
authors.initials: BJ
authors.lastname: Ku
authors.affiliation: Research Center for Drug Discovery Technology, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea; Department of Drug Development and Discovery, Graduate School of New Drug Development and Discovery, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Sang Dal
authors.identifier: 0000-0003-0620-1893
authors.initials: SD
authors.lastname: Rhee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight; D066246:ErbB Receptors / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D005951:Glucose Tolerance Test; D006529:Hepatomegaly / Q000235:genetics; D006937:Hypercholesterolemia / Q000235:genetics; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; C475819:Errfi1 protein, mouse; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D066246:ErbB Receptors; D011972:Receptor, Insulin