Selective insulin resistance in hepatocyte senescence

被引：62

作者：

Aravinthan, Aloysious ^{[1
]}

Challis, Benjamin ^{[2
]}

Shannon, Nicholas ^{[3
]}

Hoare, Matthew ^{[1
,3
]}

Heaney, Judith ^{[1
,4
]}

Alexander, Graeme J. M. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Med, Div Gastroenterol & Hepatol, Cambridge CB2 2QQ, England

[2] Univ Cambridge, Inst Metab Sci, Cambridge CB2 2QQ, England

[3] Canc Res UK Cambridge Inst, Cambridge, England

[4] Fdn Liver Res, Inst Hepatol, London, England

来源：

EXPERIMENTAL CELL RESEARCH | 2015年 / 331卷 / 01期

关键词：

Chronic liver disease; Hepatocyte senescence; Selective insulin resistance; FOXO TRANSCRIPTION FACTORS; DIABETES-MELLITUS; SIGNALING PATHWAYS; LIVER-CIRRHOSIS; HEPATITIS; GENE; REGENERATION; ASSOCIATION; PROGRESSION; INHIBITION;

D O I：

10.1016/j.yexcr.2014.09.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Ala in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：38 / 45

页数：8

共 44 条

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