ArticleAmerican journal of physiology. Endocrinology and metabolism2014
ROCK1 isoform-specific deletion reveals a role for diet-induced insulin resistance.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Unraveling the rationale and conducting a comprehensive assessment of KD025 (Belumosudil) as a candidate drug for inhibiting adipogenic differentiation-a systematic review.Naunyn-Schmiedeberg's archives of pharmacology · 2024Pooled it
- Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity.Nature communications · 2020Trial
- Advanced glycation end-products regulate extracellular matrix-adipocyte metabolic crosstalk in diabetes.Scientific reports · 2019Trial
- ROCK signaling at the crossroads of redox stress, mitochondrial dynamics, and metabolic disease.Redox biology · 2026Review
- Comprehensive microarray analysis for the identification of therapeutic targets within HIF-1α signalling networks in diet-induced obesity via hypothalamic inflammation.Archives of endocrinology and metabolism · 2025Article
- Metabolic Syndrome-Associated Erectile Dysfunction: Multiple Vascular Endothelial Dysfunction Mechanisms and Potential Therapeutic Targets.International journal of biological sciences · 2025Review
- ROCK1 deficiency preserves caveolar compartmentalization of signaling molecules and cell membrane integrity.FASEB bioAdvances · 2024Article
- Selectivity matters: selective ROCK2 inhibitor ameliorates established liver fibrosis via targeting inflammation, fibrosis, and metabolism.Communications biology · 2023Article
- CD44 Intracellular Domain: A Long Tale of a Short Tail.Cancers · 2023Review
- Targeting of G-protein coupled receptor 40 alleviates airway hyperresponsiveness through RhoA/ROCK1 signaling pathway in obese asthmatic mice.Respiratory research · 2023Article
- Insight Into Rho Kinase Isoforms in Obesity and Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Review
- Circ_0057558 promotes nonalcoholic fatty liver disease by regulating ROCK1/AMPK signaling through targeting miR-206.Cell death & disease · 2021Article
- ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2.Molecules (Basel, Switzerland) · 2021Article
- Towards an understanding of the mechanoreciprocity process in adipocytes and its perturbation with aging.Mechanisms of ageing and development · 2021Review
- Adipocyte-Derived Extracellular Vesicles: State of the Art.International journal of molecular sciences · 2021Review
- Nonalcoholic Steatohepatitis Promoting Kinases.Seminars in liver disease · 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
- Tissue-Specific Approaches Reveal Diverse Metabolic Functions of Rho-Kinase 1.Frontiers in endocrinology · 2020Review
- KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells.Adipocyte · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Rho kinase (ROCK) isoforms regulate insulin signaling and glucose metabolism negatively or positively in cultured cell lines and skeletal muscle. However, the in vivo function of the ROCK1 isoform in adipose tissue has not been addressed. To determine the specific role of the adipose ROCK1 isoform in the development of insulin resistance and obesity, mice lacking ROCK1 in adipose tissue globally or selectively were studied. Here, we show that insulin's ability to activate IRS-1/PI3K/Akt signaling was greatly enhanced in adipose tissue of ROCK1(-/-) mice compared with wild-type mice. These effects resulted from the inhibitory effect of ROCK1 on insulin receptor action, as evidenced by the fact that IR tyrosine phosphorylation was abolished in ROCK1(-/-) MEF cells when ROCK1 was reexpressed. Consistently, adipose-specific disruption of ROCK1 increased IR tyrosine phosphorylation in adipose tissue and modestly improved sensitivity to insulin in obese mice induced by high-fat feeding. This effect is independent of any changes in adiposity, number or size of adipocytes, and metabolic parameters, including glucose, insulin, leptin, and triglyceride levels, demonstrating a minimal effect of adipose ROCK1 on whole body metabolism. Enzymatic activity of ROCK1 in adipose tissue remained ∼50%, which likely originated from the fraction of stromal vascular cells, suggesting involvement of these cells for adipose metabolic regulation. Moreover, ROCK isoform activities were increased in adipose tissue of diet-induced or genetically obese mice. These data suggest that adipose ROCK1 isoform plays an inhibtory role for the regulation of insulin sensitivity in diet-induced obesity in vivo.
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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.