ArticleCell reports2022
Hepatocyte Rap1a contributes to obesity- and statin-associated hyperglycemia.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- The efficacy and safety of Chinese herbal medicine as an add-on therapy for type 2 diabetes mellitus patients with carotid atherosclerosis: An updated meta-analysis of 27 randomized controlled trials.Frontiers in pharmacology · 2023Pooled it
- Hepatocyte RAP1A Deletion Impairs Lipid Catabolism and Worsens Steatosis via Autophagy Activation.Diabetes & metabolism journal · 2026Article
- Article
- Comparative study of palmitoleic acid, sea buckthorn oil, and lovastatin in hepatocellular steatosis model.Scientific reports · 2026Article
- C3G Downregulation Enhances Stemness in Glioblastoma Cells by Promoting PKM2 Upregulation.International journal of biological sciences · 2026Article
- Deletion of C3G in hepatocytes impairs full liver maturation and alters glucose homeostasis.Cell death & disease · 2025Article
- Hepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk.Diabetes · 2025Article
- RAP1A suppresses hepatic steatosis by regulating amino acid-mediated mTORC1 activation.JHEP reports : innovation in hepatology · 2025Article
- Extracellular matrix stiffness mediates uterine repair via the Rap1a/ARHGAP35/RhoA/F-actin/YAP axis.Cell communication and signaling : CCS · 2023Article
- Prevalence and Risk Factors of Comorbid Obesity in Chinese Patients with Bipolar Disorder.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Hepatic Sam68 Regulates Systemic Glucose Homeostasis and Insulin Sensitivity.International journal of molecular sciences · 2022Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Excessive hepatic glucose production contributes to the development of hyperglycemia and is a key feature of type 2 diabetes. Here, we report that activation of hepatocyte Rap1a suppresses gluconeogenic gene expression and glucose production, whereas Rap1a silencing stimulates them. Rap1a activation is suppressed in obese mouse liver, and restoring its activity improves glucose intolerance. As Rap1a's membrane localization and activation depends on its geranylgeranylation, which is inhibited by statins, we show that statin-treated hepatocytes and the human liver have lower active-Rap1a levels. Similar to Rap1a inhibition, statins stimulate hepatic gluconeogenesis and increase fasting blood glucose in obese mice. Geranylgeraniol treatment, which acts as the precursor for geranylgeranyl isoprenoids, restores Rap1a activity and improves statin-mediated glucose intolerance. Mechanistically, Rap1a activation induces actin polymerization, which suppresses gluconeogenesis by Akt-mediated FoxO1 inhibition. Thus, Rap1a regulates hepatic glucose homeostasis, and blocking its activity, via lowering geranylgeranyl isoprenoids, contributes to statin-induced glucose intolerance.
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