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脂肪源性间充质干细胞通过调节2型糖尿病大鼠的肝脏葡萄糖代谢来改善高血糖。

Adipose-derived mesenchymal stem cells ameliorate hyperglycemia through regulating hepatic glucose metabolism in type 2 diabetic rats.

作者信息

Xie Min, Hao Hao Jie, Cheng Yu, Xie Zong Yan, Yin Ya Qi, Zhang Qi, Gao Jie Qing, Liu Hong Yu, Mu Yi Ming, Han Wei Dong

机构信息

Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China.

Institute of Basic Medicine Science, College of Life Science, Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Biochem Biophys Res Commun. 2017 Jan 29;483(1):435-441. doi: 10.1016/j.bbrc.2016.12.125. Epub 2016 Dec 21.

Abstract

Infusion of mesenchymal stem cells (MSCs) has been identified in the rapid alleviation in hyperglycemia of diabetic individuals, but the mechanism involved has not been adequately explained by these cells' potential role in modulating system insulin sensitivity and islet regeneration. In this study, we demonstrated adipose-derived mesenchymal stem cells (ASCs) produced significantly lower blood glucose via promoting hepatic glycogen synthesis and inhibiting hepatic glucose production within 24 h after infusion in T2DM rats. In vitro, HepG2 cells treated with palmitate (PA) were used as a model of hepatic glucose metabolism disorder to confirm that ASCs stimulates the phosphorylation of hepatic AMP-activated protein kinase (AMPK) to restores hepatic glucose metabolism in type 2 diabetes. In summary, this study indicated that ASCs improve hyperglycemia via regulating hepatic glucose metabolism. Additionally, the effect of ASCs on hepatic glucose metabolism depended on the AMPK signaling pathway. Thus, this is the new research of the molecular mechanisms of MSCs administration to improve glucose metabolism, and it may indicate a new treatment target of MSCs in T2DM.

摘要

输注间充质干细胞(MSCs)已被证实可快速缓解糖尿病患者的高血糖症状,但这些细胞在调节全身胰岛素敏感性和胰岛再生中的潜在作用,尚未充分解释其中涉及的机制。在本研究中,我们证明脂肪来源的间充质干细胞(ASCs)在输注到2型糖尿病(T2DM)大鼠体内后的24小时内,通过促进肝糖原合成和抑制肝糖生成,显著降低了血糖水平。在体外,用棕榈酸(PA)处理的HepG2细胞被用作肝糖代谢紊乱的模型,以证实ASCs可刺激肝AMP激活的蛋白激酶(AMPK)磷酸化,从而恢复2型糖尿病中的肝糖代谢。总之,本研究表明ASCs通过调节肝糖代谢来改善高血糖。此外,ASCs对肝糖代谢的影响依赖于AMPK信号通路。因此,这是关于间充质干细胞给药改善糖代谢分子机制的新研究,它可能为2型糖尿病中间充质干细胞的新治疗靶点指明方向。

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