Federal Grant Award Summary

Duke University received a $821,373 Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), effective June 1, 2026 through March 31, 2030. The award supports investigator-initiated basic biomedical research led by the Duke Molecular Physiology Institute examining a novel metabolic circuit in branched-chain amino acid (BCAA) catabolism and its relationship to cardiometabolic disease phenotypes. The research builds on two decades of institutional metabolomics work establishing associations between BCAA and related metabolites with chronic diseases including diabetes, insulin resistance, hepatic steatosis, and cardiac dysfunction.

The research deliverables focus on elucidating mechanistic pathways underlying BCAA metabolism through studies of branched-chain hydroxyacids (BCHA) and branched-chain ketoacids (BCKA) transport and enzymatic conversion between skeletal muscle and liver tissues. Specific research activities include identifying and characterizing hepatic enzymes responsible for BCHA-to-BCKA conversion, investigating sex-based differences in BCHA catabolism rates using stable isotope-labeled compounds, and establishing links between BCHA catabolism, hepatic amino acid metabolism, and hepatic lipid accumulation. The project will generate fundamental knowledge regarding metabolic regulation of BCAA pathways that may support future therapeutic interventions for cardiometabolic disease prevention and treatment.