Effect of hypoglycemia on brain glucose and glycogen: An in vivo carbon-13 MRS approach.

摘要

Glucose is an essential energy source for normal brain function in mammals. Glycogen as a storage form of glucose equivalent, can be used to supply glucose deficit, when in hypoglycemia or increased metabolic activity. With in vivo localized 13C MRS, non-invasive investigation of the dynamics of brain glucose and glycogen metabolism can be achieved. Previous studies suggested that, brain glucose and brain glycogen metabolism might impact the mechanism of hypoglycemia unawareness due to two observations, (1) lower glucose threshold for counterregulation in chronic hypoglycemia; (2) slower recovery from glycogen supercompensation after acute hypoglycemia. However, the physiological roles of glucose and glycogen are not fully understood.;The overall aims of this thesis were (1) to study brain glucose and glycogen metabolism during and after acute and chronic hypoglycemia; (2) to use standard biochemical assay to validate MRS methods and access total brain glycogen contents; (3) to implement chemical shift imaging method to assess glycogen distribution in the brain.;To achieve our aims, in vivo localized 13C MRS was used to assess metabolite contents and metabolisms. Standard biochemical assay was used to validate NMR quantification. Four main topics are included in this thesis. First, brain glucose and glycogen metabolism after acute hypoglycemia were studied. Second, both glucose and glycogen in the brain were further studied in chronic hypoglycemic rats. Third, MRS was validated for glucose and glycogen via biochemical assay. Finally, using chemical shift imaging method, the important role of brain glycogen after hypoglycemia was revisited when comparing with muscle glycogen.