Researchers Clarify Function Of Glucose Transport Molecule, May Lead To New Diabetes, Cancer Drugs

Researchers at the David Geffen School of Medicine at UCLA have solved the structure of a class of proteins known as sodium glucose co-transporters (SGLTs), which pump glucose into cells.

These transport proteins are used in the treatment of chronic diarrhea via oral rehydration therapy, saving the lives of millions of children each year. The solution of the SGLT structure will accelerate development of new drugs designed to treat patients with diabetes and cancer.

Led by Jeff Abramson and Ernest Wright of the UCLA Department of Physiology, the research team produced an "atomic snap shot" of an SGLT protein. Using a specialized technique known as X-ray crystallography, they and their team of post-docs and students generated the first high-resolution, three-dimensional picture of a glucose transport protein.

"This was a very challenging study that required innovation at each step of the process," said Abramson. "We literally had to invent new approaches to entice the protein into a crystal and then spent years optimizing these crystals to reach a quality suitable for visualization by X-rays. This would not have been possible without high-throughput protein production and purification capabilities."

A tantalizing observation made during the determination of the glucose transporter structure was the possibility for structural similarities with a previously crystallized neurotransmitter transporter molecule. Exploiting these similarities, along with computer modeling of structural dynamics, the researchers obtained the first atomic-level evidence for the mechanism underlying transport of glucose and neurotransmitters (such as serotonin) into cells. These results provide a fundamental understanding of how membrane proteins function in a dynamic manner.

Pharmaceutical companies already have extensive clinical trials underway to evaluate the use of inhibitors targeting SGLT1 and SGLT2 proteins to control blood glucose levels in diabetic patients by blocking intestinal glucose absorption and increasing glucose excretion into the urine. The UCLA findings will dramatically enhance the ability to rationally design these drugs.

In ongoing work, Wright and Abramson are examining the manner in which inhibitors of the transporter proteins modulate function with the goal of facilitating better drug design for the treatment of diabetes, obesity, and cancer.
University of California – Los Angeles (2008, July 3). Researchers Clarify Function Of Glucose Transport Molecule, May Lead To New Diabetes, Cancer Drugs. Journal of Science July 4th online edition.

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FACT:

Children Becoming More Vulnerable to Type 1 Diabetes: The percentage of children under 14 developing Type-1 diabetes has been going up, a new study has found. Over 6,000 Australian children aged up to 14 years developed Type-1 diabetes between 2000 and 2006, according to a report. The report indicated that the rate of such new cases was highest among children aged 10-14 years at 29 per 100,000 population.  The rate of new cases of Type-1 diabetes is rising at around three percent annually. The rate increased significantly from 19 children per 100,000 population in 2000 to 23 per 100,000 population in 2006′.in Australia. While childhood diabetes rates rose between 2000 and 2006, the rates for people aged 15-24 years remained fairly stable, but for people aged 25 or over, the rates fell. ‘This is consistent with other studies showing that the incidence is increasing among children but not among young adults. There were almost 9,000 new cases of Type-1 diabetes in people aged 15 years or over between 2000 and 2006, with males over the age of 15 almost twice as likely as females of the same age to develop the disease.

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