Janos Peti-Peterdi: Succinate and GPR91 Play Role in Diabetic Kidney Disease

A UKRO seed grant supported the Peti-Peterdi lab at the University of Southern California in performing translational studies on diabetic kidney disease, which is the number-one cause of chronic kidney disease and kidney failure. The investigator team, led by Dr. Janos Peti-Peterdi, discovered a new sensing and controlling mechanism of cell and tissue metabolism (a novel metabolic receptor) that plays a very important role in diabetes pathology in several organs.

Using genetic animal models of diabetes, along with urine samples from patients, the team generated exciting preliminary data suggesting that this new receptor is responsible for the activation of cell stress mechanisms (for example, the renin-angiotensin system, tissue fibrosis) that in the long run can cause kidney failure. In addition, the metabolic intermediate (the organic acid succinate) that accumulates in conditions of cell stress such as diabetes—and that specifically binds to the novel metabolic receptor GPR91—was also detected in the urine, and may be developed further as a biomarker or diagnostic tool of kidney damage. Renin, a hormone produced mainly by the kidneys, is another key factor in the activation of disease mechanisms that are highly active in diabetes, that increase blood pressure, and that can damage a number of organs, including the kidneys.

Thanks to the UKRO pilot grant and the newly obtained preliminary data, the Peti-Peterdi lab received an extremely competitive three-year basic research grant from the American Diabetes Association. These grants provided tremendous help for the investigator team to continue its mission to clarify the mechanistic details of kidney disease processes and to develop new drugs and therapeutic approaches for the more effective treatment of kidney disease and other related organ complications in the eyes and heart, as well as high blood pressure.

 

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