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Brain glucose transporters, O ‐GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer’s disease
Author(s) -
Liu Ying,
Liu Fei,
GrundkeIqbal Inge,
Iqbal Khalid,
Gong ChengXin
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06320.x
Subject(s) - hyperphosphorylation , glucose transporter , endocrinology , medicine , phosphorylation , transporter , alzheimer's disease , type 2 diabetes mellitus , diabetes mellitus , carbohydrate metabolism , neuroscience , tau protein , disease , biology , biochemistry , insulin , gene
Type 2 diabetes mellitus (T2DM) increases the risk for Alzheimer’s disease (AD), but the underlying mechanism is unknown. In this study, we determined the levels of major brain glucose transporters, O ‐GlcNAcylation and phosphorylation of tau in the postmortem brain tissue from frontal cortices of 7 controls, 11 T2DM subjects, 10 AD subjects and 8 additional subjects who had both T2DM and AD. We found that the neuronal glucose transporter 3 was decreased to a bigger extent in T2DM brain than in AD brain. The O ‐GlcNAcylation levels of global proteins and of tau were also decreased in T2DM brain as seen in AD brain. Phosphorylation of tau at some of the AD abnormal hyperphosphorylation sites was increased in T2DM brain. These results suggest that T2DM may contribute to the increased risk for AD by impairing brain glucose uptake/metabolism and, consequently, down‐regulation of O ‐GlcNAcylation, which facilitates abnormal hyperphosphorylation of tau.