Miller School Researchers Find Potential New Strategy for Diabetic Kidney Disease

A research team at the University of Miami Miller School of Medicine has found a potential new strategy for treating diabetic kidney disease.

“For the first time, we have identified a new lipid that is deficient in diabetic kidney disease,” said Alessia Fornoni, M.D., Ph.D., professor of medicine, chief of the Katz Family Division of Nephrology and Hypertension, and director of the Peggy and Harold Katz Family Drug Discovery Center. “By replacing that lipid, we can restore insulin signaling in kidney cells, prevent this disease from progressing, and save lives.”

Dr. Fornoni was the lead author of a study, “SMPDL3b Modulates Insulin Receptor Signaling in Diabetic Kidney Disease,” published June 19 in the journal Nature Communications. Alla Mitrofanova, Ph.D., an assistant scientist in the Department of Surgery working at the Katz Center, was the first author. Other Miller School co-authors were her long-term collaborators Sandra Merscher, Ph.D., George W. Burke, M.D., and Armando J. Mendez, Ph.D. Additional participants in the international collaborative study included Anthony Futerman, Ph.D., at the Weizmann Institute of Science in Israel, and Ingo Leibiger, Ph.D., at the Karolinska Institutet in Sweden.

Dr. Fornoni’s laboratory studies have shown that insulin resistance is an important determinant of diabetic kidney disease (DKD), a complication affecting approximately 20 to 40 percent of patients with diabetes, and leading to the need for dialysis and kidney transplantation. While managing blood glucose and high blood pressure can slow the disease progression, currently there is no cure.

During the past 10 years, Dr. Fornoni has found that insulin resistance is an important determinant of DKD.

“When kidney cells resist this hormone, they are unable to function properly,” she said. “It’s not lack of insulin production that negatively affects the kidney, but the body’s resistance that causes problems.”

The study breaks new ground by identifying a mechanism responsible for progression of DKD — a lipid enzyme called sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) that regulates the fluidity of the cellular plasma membrane.

“An excess of SMPDL3b results in the deficiency of ceramide-1 phosphate and affects the assembly and function of the insulin receptor at the plasma membranes of podocytes, which are a key cellular components of the kidney,” Dr. Fornoni said.

“If we can delete that enzyme, or replenish ceramide-1 phosphate, we can completely restore insulin signaling and protect against DKD,” she added. “This opens the door to developing a lipid therapeutic strategy to treat diabetic complications such as DKD.”


Miller School of Medicine