Metformin ameliorates skeletal muscle insulin resistance by inhibiting miR-21 expression in a high-fat dietary rat model
| Autor: | Jing Liu, Jin-Kui Yang, Jinxing Quan, Lijun Duan, Jinyang Wang, Qi Zhang, Yanbin Gao, Suhong wei, Juxiang Liu, Liming Tian |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty endocrine system diseases medicine.medical_treatment insulin resistance (IR) 03 medical and health sciences Insulin resistance Downregulation and upregulation Diabetes mellitus Internal medicine microRNA medicine luciferase reporter gene assay miRNA business.industry Insulin nutritional and metabolic diseases Skeletal muscle medicine.disease Metformin 030104 developmental biology Endocrinology medicine.anatomical_structure Oncology metformin business Homeostasis Research Paper TGF-β/Smads medicine.drug |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.20442 |
| Popis: | Insulin resistance (IR) plays a major role in the pathogenesis of abdominal obesity, hypertension, coronary heart disease, atherosclerosis and diabetes. miR-21 and TGF-β/smads is closely related to IR. However, it remained elusive whether metformin improved skeletal muscle insulin resistance (IRSM) by regulating miR-21 and its target signal TGF-β1/smads expression. In this study, high-fat diet rats with IR model and IR-skeletal muscle L6 cells (L6-SMCs) model were established, insulin sensitive index (ISI) and Homeostasis model assessment of IR (HOMA-IR) were applied, miR-21 and TGF-β1/smads mRNA expression were examined by RT-PCR, smad3 and smad7 protein were detected by western-blotting and laser scanning confocal microscopy (LSCM), the valid target of miR-21 was detected by luciferase reporter gene assay. Here, we found that metformin dose-dependently decreased miR-21 expression, accompanied by the decrease of HOMA-IR and the increase of HOMA-ISI. Luciferase report gene assay showed that smad7 was an effective target of miR-21. miR-21 overexpression directly downregulated smad7 and indirectly upregulated smad3 expression. Interestingly, miR-21 expression positively correlated with HOMA-IR and negatively correlated with HOMA-ISI. In conclusion, our results demonstrated that metformin improved IRSM by inhibiting miR-21 expression, and that miR-21 may be one of the therapeutic targets for IR. |
| Databáze: | OpenAIRE |
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