Every day, millions of people suffering from high blood cholesterol and triglyceride levels take drugs called fibrates to lower their blood lipids. Now, research conducted at City of Hope Cancer Center has revealed that these fibrates also turn off a process inside cells that causes serious complications of diabetes. This discovery could help scientists develop advanced therapeutic agents to combat these diabetic complications.
Results from the study, led by Ganesaratnam K. Balendiran, Ph.D., assistant professor, Division of Immunology, City of Hope, appear in the November 25 edition of Biochemical Pharmacology. The study reveals that several different kinds of fibrate molecules effectively shut off aldose reductase (AR), a cell enzyme that converts blood sugar (glucose) into a sugar alcohol called sorbitol.
When blood glucose is high, as with diabetes, sorbitol molecules accumulate inside cells, causing harm to the cell's integrity. Ultimately, such damage can lead to major complications including blindness (retinopathy and cataracts), nerve damage (neuropathy) and life-threatening kidney failure (nephropathy).
"For the first time, we have evidence that fibrate-like compounds shut off the aldose reductase enzyme," said Balendiran. "As fibrates are already accepted as effective lipid-lowering drugs, this discovery has significance for millions of diabetics, who commonly suffer from high blood lipids as well."
According to the U.S. Centers for Disease Control, nearly 21 million Americans have diabetes, a disease in which blood sugar levels rise to dangerous levels. Some 41 million more Americans are considered prediabetic. High blood triglycerides and cholesterol are prevalent among diabetics; in fact, two-thirds of people with diabetes die of heart attack or stroke. Additional diabetic complications such as kidney damage are not only potentially fatal, they can cause chronic suffering and diminished quality of life.
Balendiran has been designing molecules that can effectively interfere with the cell's tendency to create and accumulate unwanted sorbitol - compounds known as AR inhibitors.
"We know that aldose reductase is a critical link in a chain of events leading to serious complications of diabetes," Balendiran said. "By identifying fibrates as potent inhibitors of the enzyme, this study could help support the development of AR inhibitors that can prevent or delay these complications. The ultimate impact of this research will be in directing the design of next-generation drugs specifically targeting health problems caused by AR and related enzymes."
Sorbitol is a naturally occurring sugar alcohol which is found in apples, pears, plums and other plant-based foods. The body creates sorbitol during the metabolism of blood sugar.
The research was funded by the American Diabetes Association.
About City of Hope
City of Hope is one of the world's leading research and treatment centers for cancer, diabetes, HIV/AIDS and other life-threatening diseases. Named by U.S.News & World Report as one of America's best medical centers for cancer treatment, City of Hope is a Comprehensive Cancer Center, the highest designation bestowed by the National Cancer Institute, and a founding member of the National Comprehensive Cancer Network. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics.
City of Hope's scientific knowledge is shared with medical centers locally and globally, helping patients battling life-threatening diseases. For more information, visit cityofhope.