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Published on: May 16, 2021
The role of adipokines in skeletal muscle inflammation and insulin sensitivity
Thomas Nicholson1, Chris Church2, David J Baker2
11MRC-ARUK Centre for Musculoskeletal Ageing Research, Medical School, Queen Elizabeth Hospital, University of Birmingham, Birmingham, B15 2WB UK.
Background:
There is currently an unmet clinical need to develop better pharmacological treatments to improve glucose handling in Type II Diabetes patients with obesity. To this end, determining the effect of obesity-associated adipokines on skeletal muscle insulin sensitivity has emerged as an important area of drug discovery research. This review draws together the data on the functional role of adipokines on skeletal muscle insulin signalling, highlights several understudied novel adipokines and provides a perspective on the direction of future research.
Main Body:
The adipokines leptin, resistin, visfatin and adiponectin have all been shown to affect skeletal muscle insulin sensitivity by impacting on the activity of components within insulin signalling pathways, affecting GLUT4 translocation and modulating insulin-mediated skeletal muscle glucose uptake. Furthermore, proteomic analysis of the adipose tissue secretome has recently identified several novel adipokines including vaspin, chemerin and pref-1 that are associated with obesity and insulin resistance in humans and functionally impact on insulin signalling pathways. However, predominantly, these functional findings are the result of studies in rodents, with in vitro studies utilising either rat L6 or murine C2C12 myoblasts and/or myotubes. Despite the methodology to isolate and culture human myoblasts and to differentiate them into myotubes being established, the use of human muscle in vitro models for the functional validation of adipokines on skeletal muscle insulin sensitivity is limited.
Conclusion:
Understanding the mechanism of action and function of adipokines in mediating insulin sensitivity in skeletal muscle may lead to the development of novel therapeutics for patients with type 2 diabetes. However, to date, studies conducted in human skeletal muscle cells and tissues are limited. Such human in vitro studies should be prioritised in order to reduce the risk of candidate drugs failing in the clinic due to the assumption that rodent skeletal muscle target validation studies will to translate to human.
Insights
Obesity-associated adipokines impact skeletal muscle insulin sensitivity, crucial for type II diabetes treatment. More human studies are needed to validate findings from rodent models for drug discovery.
Area of Science:
- Endocrinology and Metabolism
- Molecular Biology
- Pharmacology
Background:
- Obesity-associated adipokines significantly influence skeletal muscle insulin sensitivity.
- There is a critical need for novel pharmacological treatments to improve glucose metabolism in Type II Diabetes patients with obesity.
Purpose of the Study:
- To review the functional roles of adipokines in skeletal muscle insulin signaling.
- To identify understudied novel adipokines and their effects.
- To provide a perspective on future research directions in this field.
Main Methods:
- Review of existing literature on adipokines (leptin, resistin, visfatin, adiponectin) and their impact on insulin signaling pathways.
- Analysis of proteomic data identifying novel adipokines (vaspin, chemerin, pref-1) associated with obesity and insulin resistance.
- Comparison of findings from rodent models and in vitro studies using rodent cell lines (L6, C2C12) with limited human skeletal muscle models.
Main Results:
- Established adipokines affect skeletal muscle insulin sensitivity by modulating insulin signaling, GLUT4 translocation, and glucose uptake.
- Novel adipokines like vaspin, chemerin, and pref-1 also impact insulin signaling pathways.
- Most functional validation studies rely on rodent models, with limited use of human skeletal muscle in vitro systems.
Conclusions:
- Understanding adipokine mechanisms in skeletal muscle insulin sensitivity can guide novel therapeutic development for type 2 diabetes.
- Current research heavily relies on rodent models, highlighting a gap in human skeletal muscle studies.
- Prioritizing human in vitro studies is essential to ensure clinical translation and reduce drug development failures.
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