Bhussry Seminar Series – “Beyond Blood Sugar: Metabolic Basis of Diabetic Kidney Disease”
Presentation: “Beyond Blood Sugar: Metabolic Basis of Diabetic Kidney Disease”
Speaker:
Subramaniam Pennathur, MD
Professor of Medicine and Molecular and Integrative Physiology
University of Michigan
Sponsored by the Department of Biochemistry and Molecular & Cellular Biology
Abstract:
Diabetes is associated with altered cellular metabolism, but how altered metabolism contributes to the development of diabetic complications, and in particular diabetic kidney disease (DKD) is unknown. We investigated changes in carbohydrate and amino acid and lipid metabolism in diabetic complication tissue including kidney cortex, peripheral nerve and retina. A systems approach using transcriptomics, metabolomics/lipidomics and metabolic flux analysis identified tissue-specific differences, in glucose, amino acid and fatty acid metabolism in the kidney. In the kidney, metabolic changes were associated with altered protein acylation and mitochondrial dysfunction. To confirm these findings in human disease, diabetic kidney transcriptomic data and metabolomics/lipidomics data were analyzed in several human cohorts. A distinct panel of lipids improved prediction of progression of DKD beyond eGFR and proteinuria when added to base model. These findings highlight an important role for altered cellular metabolism to diabetic complications and the possibility that plasma and urinary lipid and nutrient metabolites may serve as mechanistic markers of disease progression.