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Discovery of Inhibitor of Fructose Transporter Offers Novel Treatment for Diabetes and Cancer

GLUT5 inhibitor

GLUT5 inhibitor

Fructose is a naturally occurring carbohydrate. Also called fruit sugar, it is found in fruits, most root vegetables and honey and is absorbed directly into the blood stream during digestion. Commercially, fructose is extracted from sugar cane, sugar beets and corn as high-fructose corn syrup and used as a sweetener in numerous processed foods and drinks to enhance taste and browning. It is the sweetest of all the naturally occurring carbohydrates such as glucose and sucrose and cheapest to produce. As a result, many individuals consume extremely high amounts of this carbohydrate every day. Fructose consumption has increased by almost 50% among U. S. adults in the last 30 years.

When high levels of fructose are consumed, metabolic syndrome can occur, levels of glucose homeostasis can be impaired, and there can be a drastic increase in insulin resistance. Some studies show a link between a fructose-rich diet and high-blood pressure, obesity, diabetes and cancer. Many individuals are now facing these medical risks.

Fructose is transported across various cell membranes by members of the facilitated glucose transporter family of proteins called GLUTs. GLUT5 is fructose specific, and is expressed in intestine, sperm, brain, fat, skeletal muscle and kidney cells. GLUT5 is linked with various pathologies including an overexpression rate in cancer cells, meaning GLUT5 can be used as a marker for cancer. Currently, there are no known inhibitors of GLUT5 that do not interfere with the transport of glucose, which is the human body’s source of fuel. If GLUT5 specific inhibitors were discovered, they would have the potential to prevent diabetes and cancer.

Researchers from the University of New Mexico and the Rosalind Franklin University of Medicine and Science have discovered an inhibitor of GLUT5, which does not affect the glucose transport activity of other GLUTs. More specifically, this inhibitor is over 3 orders of magnitude more potent on GLUT5 compared to fructose, and achieves complete blockade of GLUT5-mediated fructose transport, with no effect on transporters GLUT1, GLUT2, GLUT3 and GLUT4. The discovery was a collaboration among Professor and Chief Tudor Oprea, Research Professor Cristian-George Bologa, and Research Assistant Professor Oleg Ursu of UNM’s Division of Translational Informatics and Associate Professor Jun-Yong Choe and Research Associate Cristina Iancu from Rosalind Franklin University’s Department of Biochemistry and Molecular Biology.

This inhibitor of GLUT5 could serve as a chemical probe to explore novel therapeutic approaches to treating obesity, diabetes and cancer. Additionally, the inhibitor is not toxic to cells and could promote new research centered around designing GLUT5-specific compounds.

STC has filed patent application(s) on this exciting new technology and is currently examining commercialization options. If you are interested in information about this or other UNM technologies, please contact Arlene Mirabal at amirabal@stc.unm.edu or 505-272-7886.