ArticleJCI insight2021
Rap1 in the VMH regulates glucose homeostasis.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Transcriptomic Analysis Reveals Molecular Mechanisms of Fleeing, Adhesion, and Thanatosis Patterns in Sea CucumberBiology · 2026Article
- Upregulation ofTranslational andrology and urology · 2026Article
- Low-dose metformin requires brain Rap1 for its antidiabetic action.Science advances · 2025Article
- Cord Blood Exosomal miRNAs from Small-for-Gestational-Age Newborns: Association with Measures of PostnatalInternational journal of molecular sciences · 2025Article
- Lard intake results in better hypothalamic leptin responsiveness than beef tallow intake during overnutrition.PloS one · 2025Article
- A Gut Microbial Transformation-Integrated Network Pharmacology Approach to Elucidate the Therapeutic Mechanisms of Timosaponin AIII in Diabetes.Current drug metabolism · 2025Article
- Fu-Fang-Qi-Di-Hua-Yu-Tang Improves Diabetic Macrovascular Disease via PI3K/AKT Pathway Regulation.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Predicting gestational diabetes mellitus risk at 11-13 weeks' gestation: the role of extrachromosomal circular DNA.Cardiovascular diabetology · 2024Article
- Article
- Exploring the molecular mechanism underlying the psoriasis and T2D by using microarray data analysis.Scientific reports · 2023Article
- Leptin signaling and its central role in energy homeostasis.Frontiers in neuroscience · 2023Review
- Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity.Science advances · 2022Article
- The ventromedial hypothalamic nucleus: watchdog of whole-body glucose homeostasis.Cell & bioscience · 2022Review
- An orally active plant Rubisco-derived peptide increases neuronal leptin responsiveness.Scientific reports · 2022Article
- Differential mRNA and long noncoding RNA expression profiles in pediatric B-cell acute lymphoblastic leukemia patients.BMC pediatrics · 2022Article
- Identification of the hub genes related to adipose tissue metabolism of bovine.Frontiers in veterinary science · 2022Article
- NR5A1 and cell population heterogeneity: Insights into developmental and functional disparities and regulatory mechanisms.Reproductive medicine and biologyReview
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The hypothalamus is a critical regulator of glucose metabolism and is capable of correcting diabetes conditions independently of an effect on energy balance. The small GTPase Rap1 in the forebrain is implicated in high-fat diet-induced (HFD-induced) obesity and glucose imbalance. Here, we report that increasing Rap1 activity selectively in the medial hypothalamus elevated blood glucose without increasing the body weight of HFD-fed mice. In contrast, decreasing hypothalamic Rap1 activity protected mice from diet-induced hyperglycemia but did not prevent weight gain. The remarkable glycemic effect of Rap1 was reproduced when Rap1 was specifically deleted in steroidogenic factor-1-positive (SF-1-positive) neurons in the ventromedial hypothalamic nucleus (VMH) known to regulate glucose metabolism. While having no effect on body weight regardless of sex, diet, and age, Rap1 deficiency in the VMH SF1 neurons markedly lowered blood glucose and insulin levels, improved glucose and insulin tolerance, and protected mice against HFD-induced neural leptin resistance and peripheral insulin resistance at the cellular and whole-body levels. Last, acute pharmacological inhibition of brain exchange protein directly activated by cAMP 2, a direct activator of Rap1, corrected glucose imbalance in obese mouse models. Our findings uncover the primary role of VMH Rap1 in glycemic control and implicate Rap1 signaling as a potential target for therapeutic intervention in diabetes.
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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 OpenQuestion graph.