1618-P: Fasting Decreases Pyruvate Carboxylase Flux in the Perfused Exocrine Pancreas

The exocrine pancreas displays structural and functional abnormalities in type 1 diabetes, such as acinar atrophy and fibrosis. Metabolic dysfunction may occur alongside these changes. We established a method to investigate exocrine metabolism using nuclear magnetic resonance (NMR) and hyperpolarized (HP) substrates. This approach conserves the native environment while permitting analysis of metabolic flux in the living pancreas. Here, we compared exocrine pancreas metabolism in fed (n=4) and fasted (n=5) male C57BL/6J mice. Each pancreas was perfused for 30 minutes with oxygenated Krebs-Heinsleit buffer in a 14 T NMR instrument. NMR spectra were collected after injection of 4 mM HP [1-13C] pyruvate into the common bile duct. 13C signals from several central carbon metabolites were detected, such as alanine, malate, and fumarate. Pancreata from fasted mice produced less (p<0.05) fumarate and aspartate compared to those from the fed mice. After perfusion, all pancreata were analyzed by gas chromatography - mass spectrometry for metabolite quantification. Malate was significantly enriched (p<0.05) by 13C in the fed pancreas with similar total malate between groups. Overall, these results suggest that the exocrine pancreas displays higher pyruvate carboxylase (PC) flux in the fed state compared to the fasted state. The methodology presented here provides a unique avenue to assess pancreatic metabolism in real-time. Disclosure A.Rushin: None. M.Mcleod: None. M.Glanz: None. D.S.Graham: None. M.Merritt: None. Funding National Institutes of Health (T32DK10876); National Science Foundation (DMR-1644779)