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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Novel aspects of adipocyte-induced skeletal muscle insulin resistance
Kristin Eckardt1, Henrike Sell, Juergen Eckel
1Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Dusseldorf, Germany. kristin.eckardt@ddz.uni-duesseldorf.de
Abstract:
Insulin resistance in skeletal muscle is an early event in the development of diabetes with obesity being one of the major contributing factors. Conditioned medium (CM) from differentiated human adipocytes impairs insulin signalling in human skeletal muscle cells. Recent data on adipocyte-induced insulin resistance in skeletal muscle cells describes underlying mechanisms of this process. Skeletal muscle insulin resistance involves multiple pathways and irreversible changes in the expression level of critical proteins. Furthermore, the reversibility of insulin resistance could be demonstrated. Several strategies to combat insulin resistance have been developed. One recent approach to treat obesity and the metabolic syndrome is the use of endocannabinoid receptor antagonists such as rimonabant. These compounds might also reduce insulin resistance in type 2 diabetes with effects on adipose tissue and liver and possibly skeletal muscle.
Insights
Obesity contributes to skeletal muscle insulin resistance, impairing glucose uptake. Endocannabinoid receptor antagonists like rimonabant show potential for treating type 2 diabetes by improving insulin sensitivity.
Area of Science:
- Metabolic disorders
- Endocrinology
- Molecular biology
Background:
- Insulin resistance in skeletal muscle is a key factor in diabetes development, often linked to obesity.
- Human adipocyte conditioned medium negatively impacts insulin signaling in skeletal muscle cells.
- Understanding adipocyte-induced insulin resistance mechanisms is crucial for metabolic health.
Purpose of the Study:
- To investigate the mechanisms of adipocyte-induced insulin resistance in skeletal muscle.
- To explore the potential of endocannabinoid receptor antagonists in combating insulin resistance.
Main Methods:
- Utilized conditioned medium from differentiated human adipocytes.
- Examined insulin signaling pathways in human skeletal muscle cells.
- Assessed the effects of endocannabinoid receptor antagonists (e.g., rimonabant).
Main Results:
- Adipocyte-derived factors impair skeletal muscle insulin signaling.
- Insulin resistance involves complex pathways and protein expression changes.
- Evidence suggests insulin resistance can be reversible.
Conclusions:
- Obesity-driven insulin resistance in skeletal muscle is a significant concern.
- Endocannabinoid receptor antagonists may offer a therapeutic strategy for type 2 diabetes and metabolic syndrome.
- Rimonabant demonstrates potential effects on adipose tissue, liver, and skeletal muscle insulin sensitivity.
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