Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease
Ian A. Simpson PhD
Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
Search for more papers by this authorKoteswara R. Chundu MD
Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
Search for more papers by this authorTheresa Davies-Hill BS
Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
Search for more papers by this authorWilliam G. Honer MD
Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, Bronx, NY
Search for more papers by this authorCorresponding Author
Dr. Peter Davies PhD
Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, Bronx, NY
Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461Search for more papers by this authorIan A. Simpson PhD
Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
Search for more papers by this authorKoteswara R. Chundu MD
Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
Search for more papers by this authorTheresa Davies-Hill BS
Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
Search for more papers by this authorWilliam G. Honer MD
Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, Bronx, NY
Search for more papers by this authorCorresponding Author
Dr. Peter Davies PhD
Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, Bronx, NY
Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461Search for more papers by this authorAbstract
Glucose metabolism is depressed in the temporal and parietal regions of the cortex in patients with Alzheimer's disease. We measured the concentrations of two glucose transporters, GLUT1 and GLUT3, in six regions of brains from both control subjects and patients with Alzheimer's disease. The concentrations of both transporters were reduced in the cerebral cortex, with larger and highly significant reductions observed for GLUT3, the putative neuronal glucose transporter. The reductions in GLUT3 were greater than the loss of synapses, and should be considered as a potential cause of the deficits in glucose metabolism.
References
- 1 Katzman R. The prevalence and malignancy of Alzheimer's disease. Ann Neurol 1976; 33: 217–218
- 2 Benson DF, Kuhl DE, Randall A, et al. The fluorodeoxyglucose 18F scan in Alzheimer's disease and multi-infarct dementia. Arch Neurol 1983; 40: 711–714
- 3 Duara R, Grady C, Haxby J, et al. Positron emission tomography in Alzheimer's disease. Neurology 1986; 36: 879–887
- 4 Friedland RP, Jagust WJ, Huesman RH, et al. Regional cerebral glucose transport and utilization in Alzheimer's disease. Neurology 1989; 39: 1427–1434
- 5 Bell GI, Kayano T, Buse JB, et al. Molecular biology of mammalian glucose transporters. Diabetes Care 1990; 13: 198–208
- 6 Mueckler M, Caruso C, Baldwin S, et al. Sequence and structure of a human glucose transporter. Science 1985; 229: 941–945
- 7 Birnbaum MJ, Haspel HC, Rosen OM. Cloning and characterization of a cDNA encoding a rat brain glucose transporter protein. Proc Natl Acad Sci USA 1986; 83: 5784–5788
- 8 Kayano T, Fukumoto H, Eddy RL, et al. Evidence for a family of human glucose transporter–like proteins: sequence and gene localization of a protein expressed in fetal skeletal muscle and other tissues. J Biol Chem 1988; 263: 15,245–15,248
- 9 Dick APK, Harik SI, Klip A, Walker DM. Identification and characterization of the glucose transporter of the blood brain barrier by cytochalasin B binding and immunological reactivity. Proc Natl Acad Sci USA 1984; 81: 7233–7237
- 10 Boado RJ, Pardridge WM. The brain-type glucose transporter mRNA is specifically expressed at the blood-brain barrier. Biochem Biophys Res Commun 1990; 166: 174–179
- 11 Pardridge WM, Boado RJ, Farrell CR. Brain-type glucose transporter (GLUT1) is specifically expressed at the blood-brain barrier. J Biol Chem 1990; 265: 18,035–18,040
- 12 Sivitz W, DeSautel S, Walker PS, Pessin JE. Regulation of glucose transporter in developing rat brain. Endocrinology 1989; 124: 1875–1880
- 13 Nagamatsu S, Kornhauser JM, Burant CF, et al. Glucose transporter expression in brain. cDNA sequence of mouse GLUT3, the brain facilitative glucose transporter isoform, and identification of sites of expression by in situ hybridization. J Biol Chem 1990; 267: 467–473
- 14 Yano H, Seino Y, Inagaki N, et al. Tissue distribution and species difference of the brain type glucose transporter (GLUT3). Biochem Biophys Res Commun 1991; 174: 470–477
- 15 Bondy C, Lee WM, Zhou J. Ontogeny and cellular distribution of brain glucose transporter gene expression. Mol Cell Neurosci 1992; 3: 305–314
- 16 Maher F, Davies-Hill T, Lysko P, et al. Expression of two glucose transporters, GLUT1 and GLUT3, in cultured cerebellar neurons: evidence for neuronal specific expression of GLUT3. Mol Cell Neurosci 1991; 2: 351–360
- 17 Khachaturian ZD. Diagnosis of Alzheimer's disease. Arch Neurol 1985; 42: 1097–2002
- 18 Terry RD, Masliah E, Salmon DP. Physical basis of cognitive alterations in Alzheimer's disease: synaptic loss is the major correlate of cognitive impairment. Ann Neurol 1991; 30: 572–580
- 19 Masliah E, Hansen L, Albright T, et al. Immunoelectron microscopic study of synaptic pathology in Alzheimer's disease. Acta Neuropathol (Berl) 1991; 81: 428–433
- 20 Masliah E, Terry RD, Alford M, DeTeresa RM. Quantitative immunohistochemistry of synaptophysin in human neocortex: an alternative method to estimate density of presynaptic terminals in paraffin sections. J Histochem Cytochem 1990; 38: 837–844
- 21 Honer WG, Dickson DW, Gleeson J, Davies P. Regional synaptic pathology in Alzheimer's disease. Neurobiol Aging 1992; 13: 375–382
- 22 Honer WG, Hu L, Davies P. Human synaptic proteins with a heterogeneous distribution in cerebellum and visual cortex. Brain Res 1993; 609: 9–20
- 23 Kalaria RN, Harik SI. Reduced glucose transporter at the blood brain barrier and in the cerebral cortex in Alzheimer's disease. J Neurochem 1989; 53: 1083–1088
- 24 Carruthers A. Facilitated diffusion of glucose. Am Physiol Soc 1990; 70: 1135–1176
- 25 Gould GW, Thomas HW, Jess TJ, Bell GI. Expression of human glucose transporters in Xenopus oocytes: kinetic characterization and substrate specificities of the erythrocyte, liver and brain isoforms. Biochemistry 1991; 30: 5139–5145
- 26 Jagust WJ, Seab JP, Huesman RH, et al. Diminished glucose transport in Alzheimer's disease: dynamic PET studies. J Cereb Blood Flow Metab 1991; 11: 323–330
- 27 Sokoloff L, Reivich M, Kennedy C, et al. The 14C deoxyglucose method for the measurement of the local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized rat. J Neurochem 1977; 28: 897–916
- 28 Crane RK, Sols A. The competitive inhibition of brain hexokinase by glucose-6-phosphate and related compounds. J Biol Chem 1954; 210: 597–606
- 29 Hawkins RA, Miller AL, Cremer JE, Veech RL. Measurement of the rate of glucose utilization by rat brain in vivo. J Neurochem 1974; 23: 917–923
- 30 Lowry OH, Passonneau JV, Hasselberger FX, Schulz DW. The relationships between substrates and enzymes of glycolysis in brain. J Biol Chem 1964; 239: 18–30
- 31 Parry DM, Pederson PC. Glucose catabolism in brain. Intracellular localization of hexokinase. J Biol Chem 1990; 265: 1059–1066
- 32 Burgess RW, Wilson JE. Hexokinase levels in discrete regions of rat brain: evaluation by quantitative immunofluorescence using interactive laser cytometry and comparison with basal rates of glucose utilization. J Neurochem 1991; 57: 441–446
- 33 Vinten J, Gliemann J, Osterlind J. Exchange of 3-O-methyl-glucose in isolated fat cells. Concentration dependence and effect of insulin. J Biol Chem 1976; 251: 794–800
- 34 Simpson IA, Cushman SW. Hormonal regulation of mammalian glucose transporters. Annu Rev Biochem 1986; 55: 1059–1089
- 35 Yki-Jrvinen H, Sahlin K, Ren JM, Koivisto VA. Localization of rate-limiting defect for glucose disposal in skeletal muscle of insulin-resistant type I diabetic patients. Diabetes 1990; 39: 157–167
- 36 Rothman DL, Shulman RG, Shulman GI. 31P nuclear magnetic resonance measurements of muscle glucose 6 phosphate: evidence for reduced insulin dependent muscle glucose transport or phosphorylation activity in non-insulin dependent diabetes mellitus. J Clin Invest 1992; 89: 1064–1075
- 37 Lewis LD, Ljunggren B, Norberg K, Siesjo BK. Changes in carbohydrate, amino acids and ammonia in the brain during insulin-induced hypoglycemia. J Neurochem 1974; 23: 659–671
- 38 Ingvar M, Siesjo BK. Pathophysiology of epileptic brain damage. In: CG Wasterlain, P Vert, eds. Neonatal seizures New York: Raven, 1990: 115–122
Citing Literature
