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New research identifies that exercise can improve insulin sensitivity in the muscles of Greenlandic Inuit individuals carrying a genetic variant that predisposes them to type 2 diabetes.
This discovery is significant because it informs targeted interventions for a high-risk group, potentially reducing the prevalence of diabetes through non-pharmacological means.
A study published by researchers from the University of Copenhagen and Steno Diabetes Center Greenland reveals that exercise is beneficial in enhancing insulin sensitivity among Greenlandic Inuit with the TBC1D4 genetic variant.
Research indicates that about 4% of Greenland's Inuit population carries a variant of the TBC1D4 gene, predisposing them to a tenfold increased risk of type 2 diabetes. This genetic mutation leads to insulin resistance in muscle tissues.
"The TBC1D4 gene variant makes them highly glucose intolerant," explains Professor Jørgen Wojtaszewski from the University of Copenhagen.
This specific form of insulin resistance is unusual because it is isolated to muscle tissue, unlike typical diabetes cases where multiple organs are involved. This isolation suggests a targeted approach in addressing this risk.
The study further reveals that even a single hour of moderate exercise can significantly improve insulin sensitivity in those with the TBC1D4 variant. Although the results are less pronounced than in non-carriers, the impact is still notable.
"A single training session involving one hour of moderate physical activity increases insulin sensitivity in the muscles of gene variant carriers," says Professor Wojtaszewski.
This finding underscores the potential of physical activity to serve as an accessible intervention for managing diabetes risk in genetically susceptible populations.
Typical diabetes treatments focus on reducing liver sugar production and overall blood sugar levels but do not enhance muscle insulin sensitivity. For TBC1D4 carriers, these interventions may result in hypoglycemia due to their normal fasting glucose and insulin levels.
Professor Wojtaszewski warns, "Since carriers of the variant do not have elevated blood sugar levels when not eating, such treatment carries a significant risk of causing dangerously low blood sugar."
This limitation highlights the need for individualized treatment strategies that consider genetic profiles, emphasizing non-pharmacological approaches like exercise.
Insights from the research suggest that targeting muscle insulin sensitivity could be a focus for new diabetes treatments. The study offers a foundation for developing drugs that could enhance insulin sensitivity similar to the effects of physical activity.
"The pharmaceutical industry is already working to identify molecules that can activate this enzyme to regulate TBC1D4 activity," notes Professor Wojtaszewski.
While these developments are in early stages, they represent a promising avenue for improving diabetes management, particularly for those with genetic predispositions.
Kristensen, J. M., et al. (2024). Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise. Nature Metabolism, 6(12), 1452-1463. https://doi.org/10.1038/s42255-024-01153-1
Moltke, I., Jorgensen, M. E., & Hansen, A. (2014). A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature, 512(7513), 190-193. https://doi.org/10.1038/nature13425