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Common herbicides and fibrates block nutrient-sensing receptor found in gut and pancreas
Date:10/9/2009

PHILADELPHIA (October 09, 2009) -- According to new research from the Monell Center and the Mount Sinai School of Medicine, certain common herbicides and lipid-lowering fibrate drugs act in humans to block T1R3, a nutrient-sensing taste receptor also present in intestine and pancreas.

Commonly used in agriculture and medicine, these chemical compounds were not previously known to act on the T1R3 receptor.

The T1R3 receptor is a critical component of both the sweet taste receptor and the umami (amino acid) taste receptor. First identified on the tongue, emerging evidence indicates that T1R3 and related taste receptors also are located on hormone-producing cells in the intestine and pancreas.

These internal taste receptors detect nutrients in the gut and trigger the release of hormones involved in the regulation of glucose homeostasis and energy metabolism.

"Compounds that either activate or block T1R3 receptors could have significant metabolic effects, potentially influencing diseases such as obesity, type II diabetes and metabolic syndrome," noted Monell geneticist and study leader Bedrich Mosinger, M.D., Ph.D.

In the study, published online in the Journal of Medicinal Chemistry, researchers tested the ability of two classes of chemical compounds to block the T1R3 receptor. The compounds fibrates and phenoxy-herbicides were selected based on their strong structural similarity to lactisole, a sweet taste inhibitor that exerts its taste effects by blocking T1R3.

Fibrates are a class of drugs frequently used to treat lipid disorders such as high blood cholesterol and triglycerides. Phenoxy-herbicides are used in agriculture to control broad-leaf weeds; the best known, 2,4-D, is one of the most extensively used herbicides worldwide.

Using an in vitro preparation, the researchers found that both classes of compounds potently blocked activation of the human sweet taste receptor, acting at m
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Contact: Leslie Stein
stein@monell.org
267-519-4707
Monell Chemical Senses Center
Source:Eurekalert

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