Hyperglycemia selectively increases cerebral non-oxidative glucose consumption without affecting blood flow.

Multiple studies have shown that hyperglycemia increases the cerebral metabolic rate of glucose (CMRglc) in subcortical white matter. This observation remains unexplained. Using positron emission tomography (PET) and pancreatic glucose clamps with basal insulin replacement in twenty-nine healthy young adults (34.5 years, SD = 10.1) we found that acute hyperglycemia increases non-oxidative CMRglc (i.e., aerobic glycolysis (AG)) in subcortical white mater as well as in medial temporal lobe structures, cerebellum and brainstem, all areas with low CMRglc during euglycemia. Surprisingly, hyperglycemia did not change regional cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO2), or the blood-oxygen-level-dependent (BOLD) response. Correlation with existing regional gene expression data showed that brain regions where CMRglc increased have greater expression of hexokinase 2 (HK2). Simulations of glucose transport revealed that, unlike hexokinase 1, HK2 is not saturated at euglycemia, and thus can accommodate increased AG during hyperglycemia.