
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.05.611035
preprint
1
Article
Hyperglycemia selectively increases cerebral non-oxidative glucose consumption without affecting blood flow
Blazey Tyler http://orcid.org/0000-0002-3402-0654

Lee John J. http://orcid.org/0000-0003-2269-6267

Snyder Abraham Z.
Goyal Manu S.
Hershey Tamara http://orcid.org/0000-0001-7549-0698

Arbeláez Ana Maria http://orcid.org/0000-0001-6977-9786

Raichle Marcus E. http://orcid.org/0000-0002-1847-9588

10 9 2024
2024.09.05.611035https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.09.05.611035
nihpp-2024.09.05.611035.pdf
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 (CMRO 2 ), 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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pmc
