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: Xiaolin Lin, Yujuan Qin, Junshuang Jia, Taoyan Lin, Xia Lin, Li Chen, Hui Zeng, Yanjiang Han, Lihong Wu, Shun Huang, Meng Wang, Shenhao Huang, Raoying Xie, Liqi Liang, Yu Liu, Ruiyu Liu, Tingting Zhang, Jing Li, Shengchun Wang, Penghui Sun, Wenhua Huang, Kaitai Yao, Kang Xu, Tao Du, Dong Xiao
• Journal: PLoS genetics (PLoS Genet) Vol. 12 Issue 10 Pg. e1006308 (Oct 2016) ISSN: 1553-7404 [Electronic] United States
• PMID: 27711113 (Publication Type: Journal Article)

Chemical References

• Insulin
• Insulin Receptor Substrate Proteins
• Irs1 protein, mouse
• MicroRNAs
• Mirn155 microRNA, mouse
• Proto-Oncogene Proteins c-akt
• Glucose

Topics

• Adipose Tissue (metabolism, pathology)
• Animals
• Cell Proliferation (genetics)
• Diabetes Mellitus, Type 2 (blood, genetics, metabolism)
• Gene Expression Regulation
• Glucose (metabolism)
• Humans
• Hyperglycemia (blood, genetics, pathology)
• Insulin (genetics, metabolism)
• Insulin Receptor Substrate Proteins (genetics)
• Insulin Resistance (genetics)
• Insulin-Secreting Cells (metabolism, pathology)
• Mice
• Mice, Transgenic
• MicroRNAs (biosynthesis, genetics)
• Muscle, Skeletal (metabolism, pathology)
• Proto-Oncogene Proteins c-akt (genetics)