Dallas, Texas - UT Southwestern Medical Center scientists have gleaned a key cellular mechanism of how the body adjusts glucose levels, an important process that when abnormal can promote diabetes, cancer, and rare genetic diseases.
The researchers determined that an enzyme called Protein Kinase C (PKC) can regulate whether more or less glucose should be transported into cells, serving as a kind of thermostat to ensure that proper levels are maintained.
“Precisely controlling glucose transport is critical to health,” said senior author Dr. Richard Wang, Assistant Professor of Dermatology and a member of UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center. “This process is defective in a variety of diseases including diabetes and cancer.”
Scientists have known how glucose is transported across cells, but had not previously understood in detail how the body controls the amount of glucose that is transported.
“Glucose transporter type 1, called GLUT1, transports glucose across the cell membrane of most cells in the body and is especially important in the uptake of glucose by the brain and blood vessels,” Dr. Wang explained. “But how GLUT1 might quickly adjust the rate of uptake was not fully understood.”
The findings appear in the journal Molecular Cell. Researchers found that GLUT1 is modified by the addition of a phosphate group by the PKC enzyme. This addition, called phosphorylation, increases the amount of GLUT1 present in the cell membrane and thereby increases the rate of glucose transport.
The researchers further found that the regulation of GLUT1 by PKC was impaired in some patients with a genetic disease called GLUT1 Deficiency Syndrome (G1D). Patients with G1D have seizures, movement disorders, speech disorders, and developmental delays as infants because insufficient glucose is transported to the brain.
“With our ongoing studies on the regulation of GLUT1 by phosphorylation, we hope to identify pathways that may improve the diagnosis and treatment of diseases, including G1D, diabetes, and cancer,” said Dr. Wang, whose lab focus includes non-melanoma skin cancer, in which GLUT1 is highly expressed.
Other UT Southwestern researchers involved include lead co-authors Eunice Lee and Dr. Jing Ma; Dr. Wentao Mi, Instructor in Neurology and Neurotherapeutics; Physiology student Nam Nguyen; Dr. Youxing Jiang, Professor of Physiology and W.W. Caruth, Jr. Scholar in Biomedical Research; Dr. Juan Pascual, Associate Professor of Neurology and Neurotherapeutics, Physiology, Pediatrics, and a member of the Eugene McDermott Center for Human Growth and Development, who holds The Once Upon a Time Foundation Professorship in Pediatric Neurologic Diseases; post-doctoral researcher Dr. Anastasia Sacharidou; Dr. Philip Shaul, Professor, Vice Chair of Research, and Chief of the Division of Pulmonary and Vascular Biology in Pediatrics, who holds the Associates First Capital Corporation Distinguished Chair in Pediatrics; and Dr. Marcel Mettlen, Assistant Professor of Cell Biology. Researchers in Pathology from the Medical College of Wisconsin also contributed.
The work was supported by the National Cancer Institute, the Burroughs Wellcome Fund, the American Cancer Society, the Harold C. Simmons Comprehensive Cancer Center, Disease Oriented Clinical Scholar Awards, and the Department of Dermatology.
UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center is the only National Cancer Institute-designated cancer center in North Texas and one of just 68 NCI-designated cancer centers in the nation. The Simmons Cancer Center includes 13 major cancer care programs with a focus on treating the whole individual with innovative treatments, while fostering groundbreaking research that has the potential to improve patient care and prevention of cancer worldwide. In addition, the Center’s education and training programs support and develop the next generation of cancer researchers and clinicians.
The Simmons Cancer Center is among only 30 U.S. cancer research centers to be named a National Clinical Trials Network Lead Academic Participating Site, a prestigious new designation by the NCI, and the only Cancer Center in North Texas to be so designated. The designation and associated funding is designed to bolster the cancer center’s clinical cancer research for adults and to provide patients access to cancer research trials sponsored by the NCI, where promising new drugs often are tested.