Adaptations in Central Carbon and Fatty Acid Metabolism in the Type 1 Diabetic Exocrine Pancreas by Magnetic Resonance

Motivation: The role of the exocrine pancreas in Type 1 Diabetes (T1D) pathophysiology is dramatically understudied. Goal(s): Our goal was to measure pyruvate metabolism and de novo lipogenesis (DNL) to determine if the exocrine pancreas displays metabolic adaptations in the context of T1D. Approach: : We utilized hyperpolarized [1-13C]pyruvate and JHSQC experiments as well as 2H spectroscopy after 2H2O administration in a mouse model of T1D to interrogate these metabolic pathways. Results: Pyruvate carboxylation was increased in the T1D exocrine pancreas with active pyruvate cycling. DNL was decreased in the liver with no significant changes in the pancreas. Impact: The consequences of pyruvate cycling and increased pyruvate carboxylation in the T1D exocrine pancreas can now be investigated, and may be a target for therapeutic intervention, whereas rates of DNL were unchanged in the T1D pancreas.