1. Academic Validation
  2. Regulation of insulin resistance by targeting the insulin-like growth factor 1 receptor with microRNA-122-5p in hepatic cells

Regulation of insulin resistance by targeting the insulin-like growth factor 1 receptor with microRNA-122-5p in hepatic cells

  • Cell Biol Int. 2019 May;43(5):553-564. doi: 10.1002/cbin.11129.
Li Dong 1 2 3 Xiaoyu Hou 1 2 Fengsui Liu 3 Hong Tao 4 Yunjia Zhang 1 2 Hang Zhao 1 2 Guangyao Song 1 5
Affiliations

Affiliations

  • 1 Department of Internal Medicine, Hebei Medical University, Shijiazhuang, 050017, Hebei, People's Republic of China.
  • 2 Key Laboratory of Metabolic Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, Hebei, People's Republic of China.
  • 3 Department of Critical Care Medicine, First Hospital of Qinhuangdao, Qinhuangdao, 066001, Hebei, People's Republic of China.
  • 4 Department of Critical Care Medicine, Qinhuangdao Hospital of Traditional Chinese Medicine, Qinhuangdao, 066006, Hebei, People's Republic of China.
  • 5 Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, People's Republic of China.
Abstract

Insulin resistance (IR) is a common etiology of type 2 diabetes (T2D) defined by a state of decreased reactivity to Insulin in multiple organs, such as the liver. This study aims to investigate how microRNA-122-5p (miR-122) regulates the hepatic IR in vitro. We first found that the miR-122 level was upregulated in the liver of rats fed with a high-fat diet and injected with streptozotocin (T2D rats), while the expression level of insulin-like growth factor 1 receptor (IGF-1R), a potential target of miR-122, was downregulated in the diabetic liver. In vitro, glucosamine-induced IR was introduced in HepG2 hepatic cells, and the levels of miR-122 and IGF-1R were further assessed. An increase of miR-122 level and a decrease of IGF-IR level were observed in IR hepatic cells, which was the same as that in the diabetic liver. Results of the luciferase reporter assay validated IGF-1R as a direct target of miR-122. Moreover, in IR HepG2 cells, antagonizing miR-122 with its specific inhibitor enhanced glucose uptake and suppressed the expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase, two key Enzymes in regulating gluconeogenesis. Such alterations induced by the miR-122 inhibitor in IR hepatic cells were impaired when IGF-1R was simultaneously knocked down. In addition, the PI3K/Akt pathway was deactivated in IR cells, and then reactivated with miR-122 inhibitor transfection. In conclusion, our study demonstrates that miR-122 is able to regulate IR in hepatic cells by targeting IGF-1R.

Keywords

PI3K/Akt pathway; gluconeogenesis; insulin resistance; insulin-like growth factor 1 receptor; microRNA-122-5p; type 2 diabetes.

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