葡萄糖稳态
平衡
胰岛素
内科学
内分泌学
胰岛素抵抗
胰岛素受体
化学
药理学
生物
医学
作者
Jinxin Liu,Chunmei Song,Chenzhipeng Nie,Yujie Sun,Yu Wang,Lamei Xue,Mingcong Fan,Haifeng Qian,Li Wang,Yan Li
出处
期刊:Phytomedicine
[Elsevier]
日期:2022-01-01
卷期号:95: 153862-153862
被引量:3
标识
DOI:10.1016/j.phymed.2021.153862
摘要
Systemic insulin signal transduction is influenced by the inter-tissue crosstalk, which might be the potential therapeutic strategy for T2DM. Although anti-diabetic function of geniposide has been previously reported, the underlying mechanism was not completely clear in light of the complex pathogenesis of T2DM.The present experiment is devoted to investigate the potential effects of geniposide on systemic insulin sensitivity mediated by hepatokine-RBP4 in high fat diet (HFD)-fed mice.The HFD-fed wild type mice were administered with geniposide (25 or 50 mg/kg/d) by intraperitoneal injection, and the normal saline and Metformin were used as negative control group and positive control group, respectively. After administration for 4 weeks, the food intake, body weight, glucose tolerance tests, insulin tolerance tests and serum biochemical indices were examined, along with insulin signaling pathway-associated proteins and hepatic histomorphological analysis. The liver, gastrocnemius and mouse primary hepatocytes were also harvested for molecular mechanism study.After geniposide treatment for 4 weeks, the blood glucose level was reduced in HFD-fed mice. Furthermore, geniposide treatment improved insulin sensitivity both in the liver and gastrocnemius (GAS). In terms of mechanism, geniposide disturbed circulating RBP4 level including its synthesis, secretion and homeostasis. Moreover, geniposide modified fuel selection and promoted glucose uptake in skeletal muscle and reduced glycogen storage, which were closely related to impaired circulating RBP4 homeostasis, leading to ameliorative systemic insulin sensitivity.Our current study proposes a novel regulatory mechanism of geniposide for improving glucose homeostasis through regulating circulating RBP4 level, which also provides new strategies for the prevention and treatment of T2DM.
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