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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
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Selective insulin resistance in hepatocyte senescence
Aloysious Aravinthan1, Benjamin Challis2, Nicholas Shannon3
1Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge, UK.
Experimental Cell Research
|September 30, 2014
Summary
Hepatocyte senescence contributes to insulin resistance in chronic liver disease. Changes in glucose transporter (GLUT) expressions in senescent liver cells serve as markers for this condition and predict poor prognosis.
Area of Science:
- Hepatology
- Metabolic Diseases
- Cellular Senescence
Background:
- Insulin resistance is a known complication of chronic liver disease.
- Hepatocyte senescence is prevalent in chronic liver disease, with up to 80% of cells exhibiting a senescent phenotype in advanced stages.
Purpose of the Study:
- To elucidate the role of hepatocyte senescence in the development of insulin resistance.
- To investigate the impact of senescence on insulin signaling and glucose transporter expression in liver cells.
Main Methods:
- Induced senescence in HepG2 cells using oxidative stress.
- Analyzed insulin metabolic pathways, including Akt signaling, AS160, and FoxO1 phosphorylation.
- Quantified GLUT2 and GLUT4 expression in senescent vs. control HepG2 cells, human cirrhotic liver tissue, and public datasets.
Main Results:
- Senescent HepG2 cells exhibited impaired insulin signaling distal to Akt, with persistent nuclear FoxO1 localization.
- Increased GLUT4 and decreased GLUT2 expression were observed in senescent cells and human cirrhotic liver tissue.
- Altered GLUT expression correlated with poor clinical prognosis in chronic liver disease cohorts.
Conclusions:
- Senescent hepatocytes develop selective insulin resistance.
- Changes in GLUT2 and GLUT4 expression can serve as surrogate markers for hepatocyte senescence in chronic liver disease.
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