title: MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice.
abstract: miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment.
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Junshuang
authors.initials: J
authors.lastname: Jia
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Taoyan
authors.initials: T
authors.lastname: Lin
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yanjiang
authors.initials: Y
authors.lastname: Han
authors.affiliation: Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Wu
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Huang
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Shenhao
authors.initials: S
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Raoying
authors.initials: R
authors.lastname: Xie
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Liqi
authors.initials: L
authors.lastname: Liang
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Shengchun
authors.initials: S
authors.lastname: Wang
authors.affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Penghui
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Anatomy, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors.forename: Kaitai
authors.initials: K
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.affiliation: Guangdong Provincial Key Laboratory of Cancer Immunotherapy Research and Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, Southern Medical University, Guangzhou, China.|Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics* / Q000473:pathology; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose