获取途径

作者

W-X. Sun K. Lou L-J. Chen S-D. Liu S-G. Pang

作者单位

Department of Pharmacy, Taishan Vocational College of Nursing, Taian, China Department of Endocrinology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China Department of Endocrinology, Shandong Rongjun General Hospital, Jinan, China

刊名

Journal of Endocrinological Investigation

ISSN

1720-8386

关键词

Lipocalin-2 Insulin sensitivity Gluconeogenesis AMP-activated protein kinase Forkhead transcription factor O1

摘要

Purpose Evidence is accumulating that lipocalin2 is implicated in insulin resistance and glucose homeostasis, but the underlying possible mechanisms remain unclear. This study is to investigate the possible linkage between LCN2 and AMP-activated protein kinase or forkhead transcription factor O1 , which influences insulin sensitivity and gluconeogenesis in liver. Methods LCN2 knockout mice and wild-type littermates were used to evaluate the effect of LCN2 on insulin sensitivity and hepatic...更多

Purpose Evidence is accumulating that lipocalin2 is implicated in insulin resistance and glucose homeostasis, but the underlying possible mechanisms remain unclear. This study is to investigate the possible linkage between LCN2 and AMP-activated protein kinase or forkhead transcription factor O1 , which influences insulin sensitivity and gluconeogenesis in liver. Methods LCN2 knockout mice and wild-type littermates were used to evaluate the effect of LCN2 on insulin sensitivity and hepatic gluconeogenesis through pyruvate tolerance test , glucose tolerance test , insulin tolerance test , and hyperinsulinemic-euglycemic clamps, respectively. LCN2KO mice and WT mice in vivo, and in vitro HepG2 cells were co-transfected with adenoviral FoxO1-siRNA or adenovirus expressing constitutively active form of AMPK , or dominant negative adenovirus AMPK , the relative mRNA and protein levels of two key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were measured. Results Improved insulin sensitivity and inhibited gluconeogenesis in the LCN2KO mice were confirmed by pyruvate tolerance tests and hyperinsulinemic-euglycemic clamps. Nuclear FoxO1 and its downstream genes PEECK and G6P were decreased in the livers of the LCN2KO mice, and AMPK activity was stimulated and directly phosphorylated FoxO1. In vitro, AMPK activity was inhibited in HepG2 cells overexpressing LCN2 leading to a decrease in phosphorylated FoxO1 and an increase in nuclear FoxO1. Conclusion The present study demonstrates that LCN2 regulates insulin sensitivity and glucose metabolism through inhibiting AMPK activity, and regulating FoxO1 and its downstream genes PEPCK/G6P, which regulate hepatic gluconeogenesis.收起

文献类型

期刊

浏览量

1