Abstract
High fructose intake is known to be associated with increased plasma triglyceride concentration, impaired glucose tolerance, insulin resistance, and high blood pressure. In addition, excess fructose intake is also thought to be a risk factor for dementia. Previous immunohistochemical studies have shown the presence of glucose transporter 5 (GLUT5), a major transporter of fructose, in the epithelial cells of the choroid plexus and ependymal cells in the brains of humans, rats, and mice, while GLUT2, a minor transporter of fructose, was localized in the ependymal cells of rat brain. In this study, immunoreactivity for the fructose transporter GLUT8 was observed in the cytoplasm of the epithelial cells in the choroid plexus and in the ependymal cells of the brains of humans and mice. These structures were not immunoreactive for GLUT7, GLUT11, and GLUT12. Our findings support the hypothesis of the transport of intravascular fructose through the epithelial cells of the choroid plexus and the ependymal cells.
References
Anderson TA (1982) Recent trends in carbohydrate consumption. Annu Rev Nutr 2:113–132
Arluison M, Quignon M, Nguyen P, Thorens B, Leloup C, Penicaud L (2004) Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain—an immunohistochemical study. J Chem Neuroanat 28:117–136
Augustin R, Riley J, Moley KH (2005) GLUT8 contains a [DE]XXXL[L1] sorting motif and localizes to a late endosomal/lysosomal compartment. Traffic 6:1196–1212
Barone S, Fussell SL, Singh AK, Lucas F, Xu J, Kim C, Wu X, Yu Y, Amlal H, Seidler U, Zuo J, Soleomani M (2009) Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension. J Biol Chem 284:5056–5066
Bouma B, Kroon-Batenburg LMJ, Wu Y-P, Brunjes B, Posthuma G, Kranenburg O, de Groot PG, Voest EE, Gebbink MFBG (2003) Glycation induces formation of amyloid cross-β structure in albumin. J Biol Chem 278:41810–41819
Cao D, Lu H, Lewis TL, Li L (2007) Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem 282:36275–36282
Cheeseman C (2008) GLUT7: a new intestinal facilitated hexose transporter. Am J Physiol Endocrinol Metab 295:E238–E241
Corpe CP, Bovelander FJ, Munoz CM, Hoekstra H, Simpson IA, Kwon O, Levine M, Burant CF (2002) Cloning and functional characterization of the mouse fructose transporter, GLUT5. Biochim Biophys Acta 1576:191–197
DeBosch BJ, Chi M, Moley KH (2012) Glucose transporter 8 (GLUT8) regulates enterocyte fructose transport and global mammalian fructose utilization. Endocrinology 153:4181–4191
Doege H, Schurmann A, Bahrenberg G, Brauers A, Joost HG (2000) GLUT8, a novel member of the sugar transport facilitator family with glucose transport activity. J Biol Chem 275:16275–16280
Douard V, Ferraris RP (2008) Regulation of the fructose transporter GLUT5 in health and disease. Am J Physiol Endocrinol Metab 295:E227–E237
Farah V, Elased KM, Chen Y, Key MP, Cunha TS, Irigoyen MC, Morris M (2006) Nocturnal hypertension in mice consuming a high fructose diet. Auton Neurosci 130:141–150
Ferder L, Ferder MD, Inserra F (2010) The role of high-fructose corn syrup in metabolic syndrome and hypertension. Curr Hypertens Rep 12:105–112
Gómez O, Romero A, Terrado J, Mesonero JE (2006) Differential expression of glucose transporter GLUT8 during mouse spermatogenesis. Reproduction 131:63–70
Greenwood CE, Winocur G (1990) Learning and memory impairment in rats fed a high saturated fat diet. Behav Neural Biol 53:74–87
Havel PJ (2005) Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev 63:133–157
Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–948
Ibberson M, Uldry M, Thorens B (2000) GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues. J Biol Chem 275:4607–4612
Jackson EE, Rendina-Ruedy E, Smith BJ, Lacombe VA (2015) Loss of toll-like receptor 4 function partially protects against peripheral and cardiac glucose metabolic derangements during a long-term high-fat diet. PLoS ONE 10(11):e0142077
Jurcovicova J (2014) Glucose transport in brain-effect of inflammation. Endocr Regul 48:35–48
Kiyasu JY, Chaikoff IL (1957) On the manner of transport of absorbed fructose. J Biol Chem 224:935–939
Korandji C, Zeller M, Guilland JC, Collin B, Lauzier B, Sicard P, Duvillard L, Goirand F, Moreau D, Cottin Y, Rochette L, Vergely C (2011) Time course of asymmetric dimethylarginine (ADMA) and oxidative stress in fructose-hypertensive rats: a model related to metabolic syndrome. Atherosclerosis 214:310–315
Kusmierz J, DeGeorge JJ, Sweeney D, May C, Rapoport SI (1989) Quantitative analysis of polyols in human plasma and cerebrospinal fluid. J Chromatogr 497:39–48
Maria Z, Campolo AR, Lacombe VA (2015) Diabetes alters the expression and translocation of the insulin-sensitive glucose transporters 4 and 8 in the atria. PLoS ONE 10(12):e0146033
Mielke JG, Taghibiglou C, Liu L, Zhang Y, Jia Z, Adeki K, Wang YT (2005) A biochemical and functional characterization of diet-induced brain insulin resistance. J Neurochem 93:1568–1578
Miller A, Adeli K (2008) Dietary fructose and the metabolic syndrome. Curr Opin Gastroenterol 24:204–209
Nualart F, Godoy A, Reinicke K (1999) Expression of the hexose transporters GLUT1 and GLUT2 during the early development of the human brain. Brain Res 824:97–104
Piroli GG, Grillo CA, Charron MJ, McEwen BS, Reagan LP (2004) Biphasic effects of stress upon GLUT8 glucose transporter expression and trafficking in the diabetic rat hippocampus. Brain Res 1006:28–35
Reagan LP, Rosell DR, Alves SE, Hoskin EK, McCall AL, Charron MJ, McEwen BS (2002) GLUT8 glucose transporter is localized to excitatory and inhibitory neurons in the rat hippocampus. Brain Res 932:129–134
Romero A, Gomez O, Terrado J, Mesonero JE (2009) Expression of GLUT8 in mouse intestine: identification of alternative spliced variants. J Cell Biochem 106:1068–1078
Salomon LL, Lanza FL, Smith DE (1961) Renal conversion of fructose to glucose. Am J Physiol 200:871–877
Schmidt S, Joost H-G, Schurmann A (2009) GLUT8, the enigmatic intracellular hexose transporter. Am J Physiol Endocrinol Metab 296:E614–E618
Singh AK, Amlal H, Haas PJ, Dringenberg U, Fussell S, Barone S, Engelhardt R, Zuo J, Seidler U, Soleimani M (2008) Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and Glut5. Kidney Int 74:438–447
Soleimani M (2011) Dietary fructose, salt absorption and hypertension in metabolic syndrome: towards a new paradigm. Acta Physiol 201:55–62
Stephan BCM, Wells JCK, Brayne C, Albanese E, Siervo M (2010) Increased fructose intake as a risk factor for dementia. J Gerontol A Biol Sci Med Sci 65:809–814
Tappy L, Le KA, Tran C, Paquot N (2010) Fructose and metabolic diseases: new findings, new questions. Nutrition 26:1044–1049
Ueno M, Nishi N, Nakagawa T, Chiba Y, Tsukamoto I, Kusaka T, Miki T, Sakamoto H, Yamaguchi F, Tokuda M (2014) Immunoreactivity of glucose transporter 5 is located in epithelial cells of the choroid plexus and ependymal cells. Neuroscience 260:149–157
White JS (2011) Proposed link between fructose intake and dementia risk is not persuasive. J Gerontol A Biol Sci Med Sci 66:537–538
Acknowledgments
This study was supported by a Grant-in-Aid for Scientific Research (C) 26430055 (M.U.) for the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The authors thank Ms. K. Yasutomi for editorial assistance.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
There is no conflict of interest.
Rights and permissions
About this article
Cite this article
Murakami, R., Chiba, Y., Tsuboi, K. et al. Immunoreactivity of glucose transporter 8 is localized in the epithelial cells of the choroid plexus and in ependymal cells. Histochem Cell Biol 146, 231–236 (2016). https://doi.org/10.1007/s00418-016-1444-5
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-016-1444-5