AI Article Synopsis
- - Sphingolipids, particularly 1-Deoxysphingolipids (dSL), are linked to insulin resistance in skeletal muscle and are found at elevated levels in individuals with obesity and type 2 diabetes compared to athletes and lean individuals.
- - The study shows that high dSL levels correlate with decreased insulin sensitivity and are associated with increased inflammation and disrupted insulin signaling in muscle cells.
- - Reducing dSL levels through weight loss and exercise improves insulin sensitivity, indicating dSL could be targeted for treatments aimed at preventing or managing type 2 diabetes.
Article Abstract
Sphingolipids are thought to promote skeletal muscle insulin resistance. 1-Deoxysphingolipids (dSL) are atypical sphingolipids that are increased in plasma of individuals with type 2 diabetes and cause β-cell dysfunction in vitro. However, their role in human skeletal muscle in unknown. We found that dSL species are significantly elevated in muscle of individuals with obesity and type 2 diabetes compared to athletes and lean individuals and are inversely related to insulin sensitivity. Furthermore, we observed a significant reduction in muscle dSL content in individuals with obesity who completed a combined weight loss and exercise intervention. Increased dSL content in primary human myotubes caused a decrease in insulin sensitivity associated with increased inflammation, decreased AMP-activated kinase (AMPK) phosphorylation, and altered insulin signaling. Our findings reveal a central role for dSL in human muscle insulin resistance and suggest dSL as therapeutic targets for the treatment and prevention of type 2 diabetes.
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| http://dx.doi.org/10.2337/db221018 | DOI Listing |
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