ArticleClinical and translational gastroenterology2019
Blunted Evoked Prouroguanylin Endocrine Secretion in Chronic Constipation.
Article in Clinical and translational gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments.Gastroenterology · 2024Review
- Fundamental Neurochemistry Review: The role of enteroendocrine cells in visceral pain.Journal of neurochemistry · 2023Review
- Guanylyl cyclase C ameliorates visceral pain: an unsuspected link.The Journal of clinical investigation · 2023Article
- 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
- Review article: diagnosis, management and patient perspectives of the spectrum of constipation disorders.Alimentary pharmacology & therapeutics · 2021Review
- Diagnosing Constipation Spectrum Disorders in a Primary Care Setting.Journal of clinical medicine · 2021Review
- Mechanisms, Evaluation, and Management of Chronic Constipation.Gastroenterology · 2020Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesProuroguanylin (ProUGN) in the intestine is cleaved to form uroguanylin (UGN), which stimulates guanylate cyclase C (GUCY2C), inducing cyclic guanosine monophosphate signaling. Paracrine release regulates fluid secretion, contributing to bowel function, whereas endocrine secretion evoked by eating forms a gut-brain axis, controlling appetite. Whereas hormone insufficiency contributes to hyperphagia in obesity, its contribution to the pathophysiology of constipation syndromes remains unexplored. Here, we compared circulating ProUGN and UGN in healthy subjects and in patients with chronic idiopathic constipation (CIC) and patients with irritable bowel syndrome with constipation (IBS-C).
methodsCirculating ProUGN and UGN levels were measured in 60 healthy subjects, 53 patients with CIC, and 54 patients with IBS-C. After an overnight fast, the participants ingested a standardized meal; blood samples were drawn at fasting and at 30, 60, and 90 minutes thereafter, and hormone levels were quantified by enzyme-linked immunosorbent assay.
resultsFasting ProUGN levels were >30% lower in patients with CIC and those with IBS-C compared with healthy subjects regardless of age, sex, or disease state. After eating, ProUGN levels increased compared with fasting levels, although the rate of change was slower and maximum levels were lower in patients with CIC and those with IBS-C. Similarly, fasting UGN levels were lower in patients with CIC and those with IBS-C compared with healthy subjects. However, unlike ProUGN levels, UGN levels did not increase after eating. DISCUSSION: These observations support a novel pathophysiologic model in which CIC and IBS-C reflect a contribution of ProUGN insufficiency dysregulating intestinal fluid and electrolyte secretion. TRANSLATIONAL IMPACT: This study suggests that CIC and IBS-C can be treated by oral GUCY2C hormone replacement. Indeed, these observations provide a mechanistic framework for the clinical utility of oral GUCY2C ligands like plecanatide (Trulance) and linaclotide (Linzess) to treat CIC and IBS-C.
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