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Abstract #0702

Detection of renal PEP-CK activity with hyperpolarized 13C-aspartate

Hikari A. I. Yoshihara1 and Juerg Schwitter2,3
1Laboratory for Functional and Metabolic Imaging, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland, 2Division of Cardiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland, 3Cardiac MR Center, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland

Renal gluconeogenesis contributes to glucose homeostasis and is elevated in diabetes. Aspartate is an efficient gluconeogenic substrate in the kidney, and its conversion to glucose proceeds via phosphoenolpyruvate carboxykinase (PEP-CK), which is a rate-limiting enzyme. Scanning the kidney of rats infused with hyperpolarized [1-13C]aspartate, the metabolites detected include [1-13C]malate and [4-13C]malate, 3-phospho[1-13C]glycerate, and a trace of bicarbonate. Using [1,4-13C2]aspartate resulted in higher bicarbonate signal, consistent with PEP-CK activity, and bicarbonate was undetectable after inhibiting PEP-CK. Compared to fed rats, the bicarbonate-to-malate ratio was 3-fold higher in fasted rats, indicating the potential of hyperpolarized aspartate to probe renal gluconeogenesis.

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