Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer's disease

• Published in: Journal of neurochemistry Vol. 111; no. 1; pp. 242 - 249
• Main Authors: Liu, Ying, Liu, Fei, Grundke-Iqbal, Inge, Iqbal, Khalid, Gong, Cheng-Xin
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2009; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - complications; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Biochemistry; Biological and medical sciences; Brain; Brain - metabolism; classification; complications; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Diabetes; diabetes mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diabetes. Impaired glucose tolerance; Down-Regulation; Down-Regulation - physiology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucose; Glucose Transport Proteins, Facilitative; Glucose Transport Proteins, Facilitative - classification; Glucose Transport Proteins, Facilitative - metabolism; glucose transporter; human brain; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Male; Medical sciences; metabolism; N-Acetylglucosaminyltransferases; N-Acetylglucosaminyltransferases - physiology; Neurology; O-GlcNAcylation; pathology; Phosphorylation; physiology; Risk factors; tau phosphorylation; tau Proteins; tau Proteins - metabolism; Endocrinopathy; Type 2 diabetes; Human; Nervous system diseases; Phosphorylation; Alzheimer disease; Central nervous system; Postmortem; Metabolic diseases; diabetes mellitus; Glucose; Metabolism; Uptake; Cerebral disorder; Encephalon; human brain; Tau protein; glucose transporter; Central nervous system disease; O-GlcNAcylation; Degenerative disease; Microtubule associated protein; tau phosphorylation; Alzheimer's disease
• ISSN: 0022-3042; 1471-4159; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06320.x

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.