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Effect of high glucose condition on glucose metabolism in primary astrocytes. Brain Res 2020 04 01;1732:146702

Date

02/08/2020

Pubmed ID

32032612

Pubmed Central ID

PMC7106974

DOI

10.1016/j.brainres.2020.146702

Scopus ID

2-s2.0-85079186997   2 Citations

Abstract

In the brain, glucose enters astrocytes through glucose transporter (GLUT1) and either enters glycolysis or the glycogen shunt. Astrocytes meet the energy needs of neurons by building up and breaking down their glycogen supply. High glucose exposure causes astrocyte dysregulation, but its effects on glucose metabolism are relatively unknown. We hypothesized that high glucose conditioning induces a glycogenic state in the astrocyte, resulting in an inefficient mobilization of substrates when challenged with glucose deprivation. Using neonatal rat astrocytes, we used normal glucose (NG, 5.5 mM) vs. high glucose (HG, 25 mM) feeding media and measured cell membrane GLUT1 expression, glucose analog uptake, glycogen content, and cellular bioenergetics. This study demonstrates that HG conditioning causes increased glucose analog uptake (p < 0.05) without affecting GLUT1 membrane expression when compared to NG conditioned astrocytes. Increased glucose uptake in HG astrocytes is associated with higher baseline glycogen content compared to NG exposed astrocytes (p < 0.05). When challenged with glucose deprivation, HG astrocytes break down more than double the amount of glycogen molecules compared to NG astrocytes, although they break down a similar percentage of the starting glycogen stores (NG = 62%, HG = 55%). Additionally, HG conditioning negatively impacts astrocyte maximal respiration and glycolytic reserve capacity assessed by the Seahorse mitochondrial stress test and glycolytic stress test, respectively (p < 0.05). These results suggest that HG conditioning shifts astrocytes towards glycogen storage at baseline. Despite increased glycogen storage, HG astrocytes demonstrate decreased metabolic efficiency and capacity putting them at higher risk during extended periods of glucose deprivation.

Author List

Staricha K, Meyers N, Garvin J, Liu Q, Rarick K, Harder D, Cohen S

Authors

Susan Cohen MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Kevin Richard Rarick PhD Assistant Professor in the Pediatrics department at Medical College of Wisconsin




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