Study Reveals How High Glucose Causes Heart, Kidney, Other Complications in Diabetes Sufferers

City of Hope
Wednesday, 21 May 2003

In a study of the genes that cause complications associated with diabetes, researchers have discovered how high glucose levels activate molecular pathways and genes, a process responsible for the high rates of heart, kidney, eye and neurological diseases that are common among people with diabetes.

Researchers at the Leslie and Susan Gonda (Goldschmied) Diabetes & Genetic Research Center at City of Hope National Medical Center said their study, which appears in the current issue of the journal Diabetes, may lead to future drug discoveries for the treatment of diabetes and its complications.

Diabetes is the seventh leading cause of death in the nation. People with diabetes are either unable to produce insulin or the insulin they produce is not effective, resulting in abnormally high glucose levels.

City of Hope researchers profiled hundreds of known genes with microarrays, the latest laboratory systems used to measure and evaluate complex scientific data.

"The results show for the first time that multiple molecules that usually play a role in inflammation and immune responses in the body are induced by high glucose via key signaling pathways," said Rama Natarajan, Ph.D., professor and chief investigator.

She said high glucose produces factors that cause distorting effects on the underlying molecular mechanisms of the body, signaling it to attack cells and tissues of the heart and circulatory system.

Natarajan said that high glucose-triggered genes and molecular processes may also result in pancreatic islet dysfunction and islet transplant rejection.

In addition to Natarajan, the research team included Narkunaraja Shanmugam, Ph.D.; Marpadga A. Reddy, Ph.D., and Mausumee Guha, Ph.D., all of the Leslie and Susan Gonda (Goldschmied) Diabetes & Research Center of Beckman Research Institute at City of Hope.

The Juvenile Diabetes Research Foundation funded the study.

City of Hope National Medical Center and Beckman Research Institute is one of the world's leading research and treatment centers for life-threatening diseases including cancer, diabetes and HIV/AIDS. Pioneering research conducted at City of Hope led to the development of a process to make human insulin in bacteria, ensuring production of unlimited quantities of human insulin and reducing costs for people with diabetes. Recombinant DNA technology developed at City of Hope led to the first product of biotechnology approved by the Food and Drug Administration, a type of synthetic insulin that is now used by more than four million people with diabetes worldwide. City of Hope is one of ten Islet Cell Resource Centers funded by the National Institutes of Health and serves as the host institution for the Southern California Islet Consortium. For more information, visit www.cityofhope.org and www.islettransplantcenter.org.

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