ArticleAmerican journal of physiology. Endocrinology and metabolism2011
In vivo activation of ROCK1 by insulin is impaired in skeletal muscle of humans with type 2 diabetes.
Article in American journal of physiology. Endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.Nature genetics · 2012Pooled it
- ROCK signaling at the crossroads of redox stress, mitochondrial dynamics, and metabolic disease.Redox biology · 2026Review
- ROCK1 regulates insulin secretion from β-cells.Molecular metabolism · 2022Article
- Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Review
- ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2.Molecules (Basel, Switzerland) · 2021Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice.Frontiers in immunology · 2021Article
- Vav2 catalysis-dependent pathways contribute to skeletal muscle growth and metabolic homeostasis.Nature communications · 2020Article
- Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1.Frontiers in endocrinology · 2020Review
- ROCK2 inhibition enhances the thermogenic program in white and brown fat tissue in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells.Adipocyte · 2019Article
- Genetic architecture of human plasma lipidome and its link to cardiovascular disease.Nature communications · 2019Article
- Review
- Lycorine Induces Mitochondria-Dependent Apoptosis in Hepatoblastoma HepG2 Cells Through ROCK1 Activation.Frontiers in pharmacology · 2019Article
- β-Actin shows limited mobility and is required only for supraphysiological insulin-stimulated glucose transport in young adult soleus muscle.American journal of physiology. Endocrinology and metabolism · 2018Article
- Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells.Scientific reports · 2018Article
- Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance.Molecular and cellular biochemistry · 2017Review
- Transition from physical activity to inactivity increases skeletal muscle miR-148b content and triggers insulin resistance.Physiological reports · 2016Article
- ROCK1 reduces mitochondrial content and irisin production in muscle suppressing adipocyte browning and impairing insulin sensitivity.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 4 countries.
Funding
Abstract
To determine whether serine/threonine ROCK1 is activated by insulin in vivo in humans and whether impaired activation of ROCK1 could play a role in the pathogenesis of insulin resistance, we measured the activity of ROCK1 and the protein content of the Rho family in vastus lateralis muscle of lean, obese nondiabetic, and obese type 2 diabetic subjects. Biopsies were taken after an overnight fast and after a 3-h hyperinsulinemic euglycemic clamp. Insulin-stimulated GDR was reduced 38% in obese nondiabetic subjects compared with lean, 62% in obese diabetic subjects compared with lean, and 39% in obese diabetic compared with obese nondiabetic subjects (all comparisons P < 0.001). Insulin-stimulated IRS-1 tyrosine phosphorylation is impaired 41-48% in diabetic subjects compared with lean or obese subjects. Basal activity of ROCK1 was similar in all groups. Insulin increased ROCK1 activity 2.1-fold in lean and 1.7-fold in obese nondiabetic subjects in muscle. However, ROCK1 activity did not increase in response to insulin in muscle of obese type 2 diabetic subjects without change in ROCK1 protein levels. Importantly, insulin-stimulated ROCK1 activity was positively correlated with insulin-mediated GDR in lean subjects (P < 0.01) but not in obese or type 2 diabetic subjects. Moreover, RhoE GTPase that inhibits the catalytic activity of ROCK1 by binding to the kinase domain of the enzyme is notably increased in obese type 2 diabetic subjects, accounting for defective ROCK1 activity. Thus, these data suggest that ROCK1 may play an important role in the pathogenesis of resistance to insulin action on glucose disposal in muscle of obese type 2 diabetic subjects.
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