Related Experiment Video
Updated: Apr 25, 2026
Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Etanercept restores normal insulin signal transduction in β2-adrenergic receptor knockout mice
Youde Jiang, Qiuhua Zhang, Eun-Ah Ye
1Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN, USA. jsteinl1@uthsc.edu.
Background:
Inhibition of TNFα protects the retina against diabetic-like changes in rodent models. The mechanism by which TNFα induces deleterious retinal changes is not known. Previously, we have shown that TNFα can inhibit normal insulin signal transduction, leading to increased apoptosis in both retinal endothelial cells (REC) and Müller cells. Additionally, β2-adrenergic receptor knockout mice (β2KO) have increased TNFα levels and decreased insulin receptor activity. In this study, we hypothesized that inhibition of TNFα in β2KO mice would increase normal insulin signaling, leading to improved retinal function.
Methods:
C57BL6 or β2KO mice were left untreated or treated with etanercept (0.3 mg/kg subcutaneously, 3× a week) for 2 months. Electroretinogram analyses were done before treatment was initiated and after two months of treatment with etanercept on all mice. Western blot or ELISA analyses were done on whole retinal lysates from all four groups of mice for TNFα, suppressor of cytokine signaling 3 (SOCS3), insulin receptor, and apoptotic proteins.
Results:
Etanercept significantly reduced TNFα levels in β2KO mice, leading to increased insulin receptor phosphorylation on tyrosine 1150/1151. SOCS3 levels were increased in β2KO mice, which were reduced after etanercept treatment. Pro-apoptotic proteins were reduced in etanercept-treated β2KO mice. Etanercept improved ERG amplitudes in β2KO mice.
Conclusions:
Inhibition of TNFα by etanercept protects the retina likely through reduced TNFα-mediated insulin resistance, leading to reduced apoptosis.
Insights
Inhibition of tumor necrosis factor-alpha (TNFα) with etanercept improved retinal function in mice lacking β2-adrenergic receptors. This treatment reduced insulin resistance and apoptosis, protecting the retina.
Area of Science:
- Ophthalmology
- Immunology
- Endocrinology
Background:
- Tumor necrosis factor-alpha (TNFα) contributes to diabetic retinopathy in rodent models.
- TNFα impairs insulin signaling and promotes apoptosis in retinal cells.
- β2-adrenergic receptor knockout (β2KO) mice exhibit elevated TNFα and reduced insulin receptor activity.
Purpose of the Study:
- To investigate if inhibiting TNFα in β2KO mice improves insulin signaling and retinal function.
- To determine the effects of etanercept on retinal TNFα levels, insulin receptor activity, and apoptosis in β2KO mice.
Main Methods:
- C57BL6 and β2KO mice were treated with etanercept or left untreated for 2 months.
- Electroretinograms (ERGs) assessed retinal function before and after treatment.
- Western blot and ELISA analyzed TNFα, SOCS3, insulin receptor, and apoptotic protein levels.
Main Results:
- Etanercept significantly decreased TNFα levels in β2KO mice.
- Insulin receptor phosphorylation and insulin signaling were increased post-etanercept treatment.
- SOCS3 and pro-apoptotic protein levels decreased, while ERG amplitudes improved in treated β2KO mice.
Conclusions:
- Etanercept protects the retina in β2KO mice by mitigating TNFα-induced insulin resistance.
- Reduced apoptosis and improved retinal function are key outcomes of TNFα inhibition.
Related Concept Videos
01:28Insulin: The Receptor and Signaling Pathways
01:25Insulin: Biosynthesis, Chemistry, and Preparation
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
01:26Type I Diabetes II: Pathophysiology