title: Exenatide reverses dysregulated microRNAs in high-fat diet-induced obese mice.
abstract: Exenatide has beneficial effects on insulin sensitivity in several animal models; however, its mechanism of action remains unclear. Furthermore, the relationship between the effect of exenatide on the changes in the relative abundance of microRNAs (miRNAs), which play a role in regulating glucose and lipid metabolism, is not fully understood. Therefore, we assessed the effect of exenatide on miRNA expression in a high-fat diet (HFD)-induced mouse model of obesity. Both HFD control and exenatide-treated HFD mice showed similar body weight gain and increase in β-cell mass. Insulin levels were significantly lower in exenatide-treated mice than in HFD control mice. The levels of miRNA-15a, 29c, 124a, and 375 in the pancreas were significantly increased in HFD control mice. Furthermore, the levels of miRNA-29c, 124a, and 146a in the liver and miRNA-15a, 29c, 124a, and 146a in the muscle were significantly increased. In contrast, the levels of miRNA-15a, 29c, 124a, and 375 in the serum were significantly decreased. These effects were reversed by treatment with exenatide. Our results provide experimental evidence that exenatide-mediated amelioration of insulin sensitivity is associated with antagonistic changes in the relative abundance of miRNA-15a, 29c, 124a, and 375 in tissues and serum, thus highlighting their usefulness as biomarkers for monitoring insulin sensitivity and response to exenatide treatment in experimental diabetes.
authors: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Ihn Suk
authors: IS
authors: Lee
authors: Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.
authors: Ki Cheol
authors: KC
authors: Park
authors: Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.
authors: Keum-Jin
authors: KJ
authors: Yang
authors: Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.
authors: Hyunsu
authors: H
authors: Choi
authors: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Yi Sun
authors: YS
authors: Jang
authors: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Jong Min
authors: JM
authors: Lee
authors: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: drkhs@catholic.ac.kr.
authors: Hye Soo
authors: HS
authors: Kim
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism*; D059305:Diet, High-Fat; D000077270:Exenatide; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D035683:MicroRNAs / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D014688:Venoms / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D035683:MicroRNAs; D010455:Peptides; D014688:Venoms; D000077270:Exenatide
keywords: Glucagon-like peptide 1; Insulin resistance; Obesity; Type 2 diabetes; microRNA