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bioRxiv · 10.1101/2024.09.05.611035

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

Blazey, T.·Lee, J. J.·Snyder, A. Z.·Goyal, M. S.·Hershey, T.·Arbelaez, A. M.·Raichle, M. E.
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Abstract

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 euinsulinaemic glucose clamps, we found, for the first time, 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 euglycemic CMRglc. 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. Regional gene expression data reveal 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, thus accommodating increased AG during hyperglycemia.

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Blazey, T., Lee, J. J., Snyder, A. Z., Goyal, M. S., Hershey, T., Arbelaez, A. M., Raichle, M. E.. 2024-09-10. Hyperglycemia selectively increases cerebral non-oxidative glucose consumption without affecting blood flow. https://doi.org/10.1101/2024.09.05.611035

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