ArticleThe Journal of clinical investigation2011
A uroguanylin-GUCY2C endocrine axis regulates feeding in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 150 citations in OpenAlex.
- Construction and Evaluation of Guanylyl Cyclase C-Specific Antibody for Noninvasive Diagnosis and Targeted Therapy of Colorectal Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Gut reactions and gut instincts: regulation of intestinal homeostasis by receptor guanylyl cyclase C (GC-C).The Biochemical journal · 2025Review
- Brain-derived uroguanylin as a regulator of postprandial brown adipose tissue activation: a potential therapeutic approach for metabolic disorders.Frontiers in pharmacology · 2025Article
- Antigen-independent activation is critical for the durable antitumor effect of GUCY2C-targeted CAR-T cells.Journal for immunotherapy of cancer · 2024Article
- GUCY2C signaling limits dopaminergic neuron vulnerability to toxic insults.NPJ Parkinson's disease · 2024Article
- Expression of guanylate cyclase C in human prefrontal cortex depends on sex and feeding status.Frontiers in molecular neuroscience · 2024Article
- Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development.Developmental cell · 2023Article
- Human α-Defensin 5International journal of molecular sciences · 2023Article
- Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development.bioRxiv : the preprint server for biology · 2023Article
- Article
- Review
- Intestinal neuropod cell GUCY2C regulates visceral pain.The Journal of clinical investigation · 2023Article
- Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery.Frontiers in endocrinology · 2023Article
- Enteroendocrine cell regulation of the gut-brain axis.Frontiers in neuroscience · 2023Review
- Guanylyl cyclase C as a diagnostic and therapeutic target in colorectal cancer.Personalized medicine · 2022Review
- Role of uroguanylin's signalling pathway in the development of ischaemic stroke.The European journal of neuroscience · 2022Article
- Neurohormonal Changes in the Gut-Brain Axis and Underlying Neuroendocrine Mechanisms following Bariatric Surgery.International journal of molecular sciences · 2022Review
- Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities.Frontiers in endocrinology · 2022Review
- A Proximal-to-Distal Survey of Healthy Adult Human Small Intestine and Colon Epithelium by Single-Cell Transcriptomics.Cellular and molecular gastroenterology and hepatology · 2022Article
- Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Intestinal enteroendocrine cells are critical to central regulation of caloric consumption, since they activate hypothalamic circuits that decrease appetite and thereby restrict meal size by secreting hormones in response to nutrients in the gut. Although guanylyl cyclase and downstream cGMP are essential regulators of centrally regulated feeding behavior in invertebrates, the role of this primordial signaling mechanism in mammalian appetite regulation has eluded definition. In intestinal epithelial cells, guanylyl cyclase 2C (GUCY2C) is a transmembrane receptor that makes cGMP in response to the paracrine hormones guanylin and uroguanylin, which regulate epithelial cell dynamics along the crypt-villus axis. Here, we show that silencing of GUCY2C in mice disrupts satiation, resulting in hyperphagia and subsequent obesity and metabolic syndrome. This defined an appetite-regulating uroguanylin-GUCY2C endocrine axis, which we confirmed by showing that nutrient intake induces intestinal prouroguanylin secretion into the circulation. The prohormone signal is selectively decoded in the hypothalamus by proteolytic liberation of uroguanylin, inducing GUCY2C signaling and consequent activation of downstream anorexigenic pathways. Thus, evolutionary diversification of primitive guanylyl cyclase signaling pathways allows GUCY2C to coordinate endocrine regulation of central food acquisition pathways with paracrine control of intestinal homeostasis. Moreover, the uroguanylin-GUCY2C endocrine axis may provide a therapeutic target to control appetite, obesity, and metabolic syndrome.
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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.