What is it about?
In the study, a new molecule was found to be important for insulin's effects in skeletal muscle. The molecule, Rho guanine nucleotide dissociation inhibitor α (RhoGDIα), slowed down muscle glucose uptake and hindered insulin's effect. Through detailed studies, the researchers found that RhoGDIα inhibited the activity of another molecule essential for muscle glucose uptake, called Rac1. Under the influence of insulin, RhoGDIα was phosphorylated and Rac1 released, which allowed the uptake of glucose into muscle cells. By reducing RhoGDIα levels through siRNA technology, they increased Rac1 activity and improved glucose uptake. Conversely, higher levels of RhoGDIα in muscle cells of experimental mice reduced glucose uptake in response to insulin, worsening overall blood glucose control. These findings confirm the negative impact of RhoGDIα on insulin sensitivity. Interestingly, the researchers also observed increased protein content of RhoGDIα in skeletal muscle of patients with type 2 diabetes and insulin resistance.
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Why is it important?
Our blood sugar is controlled by insulin, a vital hormone that regulates sugar uptake in our muscles. When insulin doesn't work properly, it leads to diabetes and increases the risk of heart diseases. The molecular events that control sugar uptake in muscles have great potential for treating insulin resistance in conditions like obesity, diabetes, and cancer. This discovery highlights RhoGDIα as a significant regulator of insulin sensitivity and blood glucose in skeletal muscle by affecting Rac1 activity
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This page is a summary of: The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action, Proceedings of the National Academy of Sciences, June 2023, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2211041120.
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