Henk M. De Feyter1, Kevin Behar1, Lester R. Drewes2, Robin A. de Graaf1, Douglas L. Rothman1
1Diagnostic Radiology, Yale University, New Haven, CT, United States; 2Biochemistry & Molecular Biology, University of Minnesota, Duluth, MN, United States
Repetitive iatrogenic hypoglycemic events lead to brain adaptations resulting in failing counterregulatory response and lack of warning symptoms (hypoglycemia unawareness) normally associated with low blood glucose levels. Increased blood-brain barrier lactate transport via upregulated monocarboxylic acid transporter 1 (MCT1) has been suggested as an adaptation induced by repetitive hypoglycemia. Increased lactate uptake and oxidation could (partially) replace glucose thereby contribute to hypoglycemia unawareness and failing counterregulatory response. We used 1H-[13C] MRS combined with [3-13C]-lactate infusion during hypoglycemia to investigate the role of increased lactate transport and/or metabolism in the brain of a rat model with ketogenic diet-induced upregulation of MCT1.