• Shuyue Wang, Huihan Ai, Lei Liu, Xiaojun Zhang, Feng Gao, Lihua Zheng, Jingwen Yi, Luguo Sun, Chunlei Yu, Huiying Zhao, and Yuxin Li.
• National Engineering Laboratory for Druggable Gene and Protein Screening, School of Life Sciences, Northeast Normal University, Changchun, China.
• Am. J. Physiol. Endocrinol. Metab. 2019 Nov 1; 317 (5): E911-E924.

AbstractIn the context of hepatic insulin resistance, hepatic gluconeogenesis is abnormally increased, which results in increased hepatic glucose production and hyperglycemia, but the underlying mechanisms remain to be fully elucidated. Micro-RNAs (miRNAs) have been identified as critical regulators of diabetes and other metabolic disorders. In this study, we found that the expressions of miRNA-27 family members miRNA-27a and miRNA-27b (miR-27a/b) decreased significantly in the livers of diabetic mice. Moreover, the levels of miR-27a/b increased in the serum of patients with type 2 diabetes. Our present results showed that inhibition of miR-27a/b expression led to increased hepatic protein levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase and enhanced hepatic gluconeogenesis in vitro and in vivo. Overexpression of miR-27a/b suppressed hepatic glucose output and alleviated hyperglycemia in diabetic mice. Further study revealed that forkhead box O1 (FOXO1) is a downstream target of miR-27a/b. Taken together, we found novel evidence suggesting that miR-27a/b contributes to hepatic gluconeogenesis through targeting FOXO1 and provided novel mechanistic insight into the pathophysiology of insulin resistance.

28 keywords...

hide…