MicroRNA-802 regulates hepatic insulin sensitivity and glucose metabolism

Yun-Feng Zhen; Yun-Jia Zhang; Hang Zhao; Hui-Juan Ma; Guang-Yao Song

MicroRNA-802 regulates hepatic insulin sensitivity and glucose metabolism

Int J Clin Exp Pathol. 2018 May 1;11(5):2440-2449. eCollection 2018.

Authors

Yun-Feng Zhen^{1

2}, Yun-Jia Zhang¹, Hang Zhao¹, Hui-Juan Ma^{1

3}, Guang-Yao Song^{1

2

3}

Affiliations

¹ Department of Internal Medicine, Hebei Medical University Shijiazhuang 050017, Hebei Province, China.
² Department of Endocrinology, Hebei General Hospital Shijiazhuang 050051, Hebei Province, China.
³ Department of Hebei Key Laboratory of Metabolic Disease, Hebei General Hospital Shijiazhuang 050051, Hebei Province, China.

PMID: 31938356
PMCID: PMC6958293

Abstract

The expression level of microRNA-802 (miR-802) is increased in livers of high-fat diet (HFD)-fed mice and obese human subjects; however, the function of miR-802 in the development of obesity-associated insulin resistance remains incompletely understood. Here we studied the potential role of miR-802 in regulating hepatic glucose metabolism and insulin sensitivity. Mice were fed either a standard chow diet or HFD for 12 weeks, and then the HFD mice were infected by injection with an adeno-associated virus expressing miR-802 or miR-802-SP. Six weeks after the injection, we measured blood glucose, plasma insulin, and insulin sensitivity in the mice. In addition, hepatic glucose levels and PI3K-Akt pathway gene expression were analyzed. Adeno-associated viral-mediated overexpression of miR-802 in the livers of HFD mice caused impaired glucose homeostasis and insulin sensitivity, thus giving rise to decreased protein level of pAkt^s473 and pPI3K, and increased protein levels of pPTEN, G6PC, and GluT2. In contrast, loss of miR-802 function in the liver of HFD mice led to increased pAkt^s473 and pPI3K, and decreased levels of pPTEN, G6PC, and GluT2, thereby improving glucose metabolism and insulin resistance. Our findings confirmed MiR-802 as a regulator of liver glucose metabolism and insulin signaling.

Keywords: glucose metabolism; hepatic; high-fat diet; insulin resistance; microRNA-802.