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Last Updated: Feb 19, 2013 - 1:22:36 AM
Research Article
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Latest Research : Gastroenterology

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Weight loss by targeting satiety hormone

Aug 27, 2011 - 7:40:40 PM , Reviewed by: Dr. Sanjukta Acharya

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[RxPG] The number of people who are obese and suffer one or more of its associated health problems (including type 2 diabetes) is escalating dramatically. Researchers are seeking to identify new targets for therapeutics that could limit appetite and thereby obesity. A team of researchers, led by Scott Waldman, at Thomas Jefferson University, Philadelphia, has now uncovered one such potential target by studying the molecular control of appetite in mice.

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. The researchers showed that silencing of GUCY2C in mice disrupts satiation, resulting in hyperphagia. This caused obesity and metabolic syndrome. In the study, Waldman and colleagues found that nutrient intake by mice caused cells in their gut to secrete the precursor of the hormone uroguanylin (prouroguanylin) into the blood. This travelled around the blood and was converted to uroguanylin in a region of the brain known as the hypothalamus, which is well known to be involved in decreasing appetite. The active uroguanylin was then found to bind to proteins on nerve cells known as GUCY2C receptors, triggering a cascade of events that led to decreased food intake.

The uroguanylin-GUCY2C endocrine axis may provide a therapeutic target to control appetite, obesity, and metabolic syndrome.



Publication: Journal of Clinical Investigation doi:10.1172/JCI57925

Funding information and declaration of competing interests: These studies were supported by grants from NIH and Targeted Diagnostics and Therapeutics. Scott A. Waldman is the Chair of the Data Safety Monitoring Board for the C-Cure Trial sponsored by Cardio3 Biosciences and the Chair (uncompensated) of the Scientific Advisory Board to Targeted Diagnostics and Therapeutics Inc., which provided research funding that, in part, supported this work and has a license to commercialize inventions related to this work.
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 About Dr. Sanjukta Acharya
This news story has been reviewed by Dr. Sanjukta Acharya before its publication on RxPG News website. Dr. Sanjukta Acharya, MBBS MRCP is the chief editor for RxPG News website. She oversees all the medical news submissions and manages the medicine section of the website. She has a special interest in nephrology. She can be reached for corrections and feedback at [email protected]
RxPG News is committed to promotion and implementation of Evidence Based Medical Journalism in all channels of mass media including internet.
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