ArticleProceedings of the National Academy of Sciences of the United States of America2023
The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Review
- Mechanical Signaling in the Microenvironment Regulates the Differentiation of Dental Pulp Stem Cells: A Novel Strategy For Pulp-Dentin Complex Regeneration.Stem cell reviews and reports · 2026Review
- Review
- Inhibition of Unc119b improves insulin sensitivity through potentiation of Rac1 activation in skeletal muscle and brown adipose tissue.Molecular metabolism · 2025Article
- The insulin signalling network.Nature metabolism · 2025Review
- Progress in Understanding the Regulation of Glucose and Fructose Metabolism.Annual review of nutrition · 2025Review
- β2-Chimaerin, a GTPase-Activating Protein for Rac1, Is a Novel Regulator of Hepatic Insulin Signaling and Glucose Metabolism.Molecules (Basel, Switzerland) · 2024Article
- Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 5 countries.
Funding
Abstract
The molecular events governing skeletal muscle glucose uptake have pharmacological potential for managing insulin resistance in conditions such as obesity, diabetes, and cancer. With no current pharmacological treatments to target skeletal muscle insulin sensitivity, there is an unmet need to identify the molecular mechanisms that control insulin sensitivity in skeletal muscle. Here, the Rho guanine dissociation inhibitor α (RhoGDIα) is identified as a point of control in the regulation of insulin sensitivity. In skeletal muscle cells, RhoGDIα interacted with, and thereby inhibited, the Rho GTPase Rac1. In response to insulin, RhoGDIα was phosphorylated at S101 and Rac1 dissociated from RhoGDIα to facilitate skeletal muscle GLUT4 translocation. Accordingly, siRNA-mediated RhoGDIα depletion increased Rac1 activity and elevated GLUT4 translocation. Consistent with RhoGDIα's inhibitory effect, rAAV-mediated RhoGDIα overexpression in mouse muscle decreased insulin-stimulated glucose uptake and was detrimental to whole-body glucose tolerance. Aligning with RhoGDIα's negative role in insulin sensitivity, RhoGDIα protein content was elevated in skeletal muscle from insulin-resistant patients with type 2 diabetes. These data identify RhoGDIα as a clinically relevant controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis, mechanistically by modulating Rac1 activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.