Skip to main content
SpringerLink
Log in

Glucose- and Fructose-Induced Toxicity in the Liver and Brain

  • Chapter
  • First Online:
Metabolic Syndrome

Abstract

Glucose is metabolized by visceral organs and brain for producing energy. In contrast, fructose is primarily metabolized by the liver. Unlike glucose, fructose is not utilized by the brain and does not stimulate insulin secretion due to its hepatic metabolism and the low level of expression of the fructose transporter GLUT5 in pancreatic β-cells. Metabolism of fructose differs from glucose due to the involvement of different transporters and enzymes. Although enzymes of glucose metabolism are efficiently regulated by ATP, but fructokinase, the enzyme that generates fructose-1-phosphate is not regulated by ATP. A high flux of fructose to the liver perturbs glucose metabolism and glucose uptake pathways leading to a significant enhancement in the rate of de novo lipogenesis and triglyceride (TAG) synthesis. These metabolic alterations may be responsible for the induction of insulin resistance and dyslipidemia. The phosphorylation of fructose also leads to ATP deletion and increase in AMP levels, which is metabolized to uric acid, a metabolite that may promote hypertension. High levels of fructose also promote the generation of advanced glycation end products (AGEs). These abnormalities contribute to the pathogenesis of oxidative stress in obesity, diabetes, MetS, fatty liver disease, cardiovascular diseases, and neurological disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ahmed N (2005) Advanced glycation endproducts—role in pathology of diabetic complications. Diabetes Res Clin Pract 67:3–21

    PubMed  CAS  Google Scholar 

  • Alexander MC, Lomanto M, Nasrin N, Ramaika C (1988) Insulin stimulates glyceraldehyde-3-phosphate dehydrogenase gene expression through cis-acting DNA sequences. Proc Natl Acad Sci USA 85:5092–5096

    PubMed  CAS  Google Scholar 

  • Alper AB Jr, Chen W, Yau L, Srinivasan SR, Berenson GS, Hamm LL (2005) Childhood uric acid predicts adult blood pressure: the Bogalusa Heart Study. Hypertension 45:34–38

    PubMed  CAS  Google Scholar 

  • Arnlov J, Vessby B, Riserus U (2004) Coffee consumption and insulin sensitivity. JAMA 291:1199–1201

    PubMed  Google Scholar 

  • Arumugam T, Simeone DM, Schmidt AM, Logsdon CD (2004) S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). J Biol Chem 279:5059–5065

    PubMed  CAS  Google Scholar 

  • Asipu A, Hayward BE, O’Reilly J, Bonthron DT (2003) Properties of normal and mutant recombinant human ketohexokinases and implications for the pathogenesis of essential fructosuria. Diabetes 52:2426–2432

    PubMed  CAS  Google Scholar 

  • Avena NM, Rada P, Hoebel BG (2006) Sugar bingeing in rats. Curr Protoc Neurosci Chapter 9:Unit9.23C

    Google Scholar 

  • Avena NM, Rada P, Hoebel BG (2008) Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev 32:20–39

    PubMed  CAS  Google Scholar 

  • Baker JF, Krishnan E, Chen L, Schumacher HR (2005) Serum uric acid and cardiovascular disease: recent developments, and where do they leave us? Am J Med 118:816–826

    PubMed  CAS  Google Scholar 

  • Barberger-Gateau, Samieri C, Féart C, Plourde M (2011) Dietary omega 3 polyunsaturated fatty acids and Alzheimer’s disease: interaction with apolipoprotein E genotype. Curr Alzheimer Res 8:479–491

    PubMed  CAS  Google Scholar 

  • Basciano H, Federico L, Adeli K (2005) Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond) 2:5

    Google Scholar 

  • Beisswenger PJ, Howell SK, Smith K, Szwergold BS (2003) Glyceraldehyde-3-phosphate dehydrogenase activity as an independent modifier of methylglyoxal levels in diabetes. Biochim Biophys Acta 1637:98–106

    PubMed  CAS  Google Scholar 

  • Benton CS, Miller BH, Skwerer S, Suzuki O, Schultz LE, Cameron MD, Marron JS, Pletcher MT, Wiltshire T (2011) Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains. Psychopharmacology (Berl) 221:297–315

    Google Scholar 

  • Bierhaus A, Fleming T, Stoyanov S, Leffler A, Babes A, Neacsu C, Sauer SK, Eberhardt M, Schnölzer M, Lasitschka F, Neuhuber WL, Kichko TI, Konrade I, Elvert R, Mier W, Pirags V, Lukic IK, Morcos M, Dehmer T, Rabbani N, Thornalley PJ, Edelstein D, Nau C, Forbes J, Humpert PM, Schwaninger M, Ziegler D, Stern DM, Cooper ME, Haberkorn U, Brownlee M, Reeh PW, Nawroth PP (2012) Methylglyoxal modification of Na(v)1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy. Nat Med 18:926–933

    PubMed  CAS  Google Scholar 

  • Bray GA, Nielsen SJ, Popkin BM (2004) Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 79:537–543

    PubMed  CAS  Google Scholar 

  • Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820

    PubMed  CAS  Google Scholar 

  • Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625

    PubMed  CAS  Google Scholar 

  • Castrogiovanni D, Alzamendi A, Ongaro L, Giovambattista A, Gaillard RC, Spinedi E (2012) Fructose rich diet-induced high plasminogen activator inhibitor-1 (PAI-1) production in the adult female rat: protective effect of progesterone. Nutrients 4:1137–1150

    PubMed  CAS  Google Scholar 

  • Cha SH, Wolfgang M, Tokutake Y, Chohnan S, Lane MD (2008) Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake. Proc Natl Acad Sci USA 105:16871–16875

    PubMed  CAS  Google Scholar 

  • Chaney MO, Stine WB, Kokjohn TA, Kuo YM, Esh C, Rathman A, Luehr DC, Schmidt AM, Stern D, Yan SD, Roher AE (2005) RAGE and amyloid β interactions: atomic force microscopy and molecular modeling. Biochim Biophys Acta 1741:199–205

    PubMed  CAS  Google Scholar 

  • Chang KC, Liang JT, Tseng CD, Wu C-D, Hsu K-L, Wu M-S, Lin Y-T, Tseng T (2007) Aminoguanidine prevents fructose-induced deterioration in left ventricular-arterial coupling in Wistar rats. Br J Pharmacol 151:341–346

    PubMed  CAS  Google Scholar 

  • Chang T, Untereiner A, Liu J, Wu L (2010) Interaction of methylglyoxal and hydrogen sulfide in rat vascular smooth muscle cells. Antioxid Redox Signal 12:1093–1100

    PubMed  CAS  Google Scholar 

  • Charonis AS, Reger LA, Dege JE, Kouzi-Koliakos K, Furcht LT, Wohlhueter RM, Tsilibary EC (1990) Laminin alterations after in vitro nonenzymatic glycosylation. Diabetes 39:807–814

    PubMed  CAS  Google Scholar 

  • Choi HK, Willett W, Curhan G (2007) Coffee consumption and risk of incident gout in men: a prospective study. Arthritis Rheum 56:2049–2055

    PubMed  CAS  Google Scholar 

  • Cirillo P, Sato W, Reungjui S, Heinig M, Gersch M, Sautin Y, Nakagawa T, Johnson RJ (2006) Uric acid, the metabolic syndrome, and renal disease. J Am Soc Nephrol 17:S165–S168

    PubMed  CAS  Google Scholar 

  • Cirillo P, Gersch M, Mu W, Scherer PM, Kim KM, Gesualdo L, Henderson GN, Johnson RJ, Sautin YY (2009) Ketohexokinase-dependent proinflammatory effect of fructose in human proximal tubular cells. J Am Soc Nephrol 20:545–553

    PubMed  CAS  Google Scholar 

  • Convit A (2005) Links between cognitive impairment in insulin resistance: an explanatory model. Neurobiol Aging 26(Suppl 1):31–35

    PubMed  Google Scholar 

  • Cox CL, Stanhope KL, Schwarz JM, Graham JL, Hatcher B, Griffen SC, Bremer AA, Berglund L, McGahan JP, Havel PJ, Keim NL (2012) Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women. Eur J Clin Nutr 66:201–208

    PubMed  CAS  Google Scholar 

  • Craft S (2009) The role of metabolic disorders in Alzheimer disease and vascular dementia: two roads converged. Arch Neurol 66:300–305

    PubMed  Google Scholar 

  • Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, Castellano A, Pifferi F, Bocti C, Paquet N, Begdouri H, Bentourkia M, Turcotte E, Allard M, Barberger-Gateau P, Fulop T, Rapoport SI (2011) Brain fuel metabolism, aging, and Alzheimer’s disease. Nutrition 27:3–20

    PubMed  CAS  Google Scholar 

  • Curry DL (1989) Effects of mannose and fructose on the synthesis and secretion of insulin. Pancreas 4:2–9

    PubMed  CAS  Google Scholar 

  • De Fronzo RA (1981) The effect of insulin on renal sodium metabolism. A review with clinical implications. Diabetologia 21:165–171

    Google Scholar 

  • De Fronzo RA (1997) Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev 5:177–269

    Google Scholar 

  • Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ, Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension (2005) Endothelial function and dysfunction. Part I: methodological issues for assessment in the different vascular beds: a statement by the working group on endothelin and endothelial factors of the European society of hypertension. J Hypertens 23:7–17

    PubMed  CAS  Google Scholar 

  • Deshmukh R, Smith A, Lilly LS (1998) Hypertension. In: Lilly LS (ed) Pathophysiology of heart disease, 2nd edn. Lippincott Williams and Wilkins, Philadelphia, PA, pp 267–288

    Google Scholar 

  • Dhar A, Dhar I, Jiang B, Desai KM, Wu L (2011) Chronic methylglyoxal infusion by minipump causes pancreatic beta cell dysfunction and induces type 2 diabetes in Sprague-Dawley rats. Diabetes 60:899–908

    PubMed  CAS  Google Scholar 

  • Diggle CP, Shires M, Leitch D, Brooke D, Carr IM, Markham AF, Hayward BE, Asipu A, Bonthron DT (2009) Ketohexokinase: expression and localization of the principal fructose-metabolizing enzyme. J Histochem Cytochem 57:763–774

    PubMed  CAS  Google Scholar 

  • Distler MG, Plant LD, Sokoloff G, Hawk AJ, Aneas I, Wuenschell GE, Termini J, Meredith SC, Nobrega MA, Palmer AA (2012) Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal. J Clin Invest 122:2306–2315

    PubMed  CAS  Google Scholar 

  • Dou JT, Chen M, Dufour F, Alkon DL, Zhao WQ (2005) Insulin receptor signaling in long-term memory consolidation following spatial learning. Learn Mem 12:646–655

    PubMed  Google Scholar 

  • Du X, Matsumura T, Edelstein D, Rossetti L, Zsengeller Z, Szabo C, Brownlee M (2003) Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J Clin Invest 112:1049–1057

    PubMed  CAS  Google Scholar 

  • Dyck JR, Lopaschuk GD (2006) AMPK alterations in cardiac physiology and pathology: enemy or ally? J Physiol 574:95–112

    PubMed  CAS  Google Scholar 

  • Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ (2002) Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr 76:911–922

    PubMed  CAS  Google Scholar 

  • Fages C, Nolo R, Huttunen HJ, Eskelinen E, Rauvala H (2000) Regulation of cell migration by amphoterin. J Cell Sci 113:611–620

    PubMed  CAS  Google Scholar 

  • Fang F, Lue LF, Yan S, Xu H, Luddy JS, Chen D, Walker DG, Stern DM, Yan S, Schmidt AM, Chen JX, Yan SS (2010) RAGE-dependent signaling in microglia contributes to neuroinflammation, Abeta accumulation, and impaired learning/memory in a mouse model of Alzheimer’s disease. FASEB J 24:1043–1055

    PubMed  CAS  Google Scholar 

  • Farah V, Elased KM, Chen Y, Key MP, Cunha TS, Ingoyen M, Morris M (2006) Nocturnal hypertension in mice consuming a high fructose diet. Auton Neurosci 130:41–50

    PubMed  CAS  Google Scholar 

  • Farooqui AA, Farooqui T, Panza F, Frisardi V (2012) Metabolic syndrome as a risk factor for neurological disorders. Cell Mol Life Sci 69:741–762

    PubMed  CAS  Google Scholar 

  • Freemantle E, Vandal M, Tremblay-Mercier J, Plourde M, Poirier J, Cunnane S (2009) Metabolic response to a ketogenic breakfast in the healthy elderly. J Nutr Health Aging 13:293

    PubMed  CAS  Google Scholar 

  • Frisoli TM, Schmieder RE, Grodzicki T, Messerli FH (2011) Beyond salt: lifestyle modifications and blood pressure. Eur Heart J 32:3081–3087

    PubMed  Google Scholar 

  • Froesch ER (1972) Fructose metabolism in adipose tissue. Acta Med Scand Suppl 542:37–46

    PubMed  CAS  Google Scholar 

  • Funk SD, Yurdogul A Jr, Orr W (2012) Hyperglycemia and endothelial dysfunction in atherosclerosis: lessons from type 1 diabetes. Int J Vasc Med 2012:569654

    PubMed  Google Scholar 

  • Furlong J (1996) Acetyl-L-carnitine: metabolism and applications in clinical practice. Altern Med Rev 1:85–93

    Google Scholar 

  • Gagliardi ACM, Miname MH, Santos RD (2009) Uric acid: a marker of increased cardiovascular risk. Atherosclerosis 202:11–17

    PubMed  CAS  Google Scholar 

  • Gao X, Qi L, Qiao N, Choi HK, Curhan G, Tucker KL, Ascherio A (2007) Intake of added sugar and sugar-sweetened drink and serum uric acid concentration in US men and women. Hypertension 50:306–312

    PubMed  CAS  Google Scholar 

  • Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070

    PubMed  CAS  Google Scholar 

  • Goldin A, Beckman JA, Schmidt AM, Creager MA (2006) Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114:597–605

    PubMed  CAS  Google Scholar 

  • Gong Z, Muzumdar RH (2012) Pancreatic function, Type 2 diabetes, and metabolism in aging. Int J Endocrinol PMC 3362843

    Google Scholar 

  • Hallfrisch J (1990) Metabolic effects of dietary fructose. FASEB J 4:2652–2660

    PubMed  CAS  Google Scholar 

  • Havel PJ (2002) Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 13:51–59

    PubMed  CAS  Google Scholar 

  • Havel PJ (2005) Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev 63:133–157

    PubMed  Google Scholar 

  • Hayward BE, Bonthron DT (1998) Structure and alternative splicing of the ketohexokinase gene. Eur J Biochem 257:85–91

    PubMed  CAS  Google Scholar 

  • Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC (2009) Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond) 6:31

    Google Scholar 

  • Heo SH, Lee SH (2010) High levels of serum uric acid are associated with silent brain infarction. J Neurol Sci 297:6–10

    PubMed  CAS  Google Scholar 

  • Higai K, Shimamura A, Matsumoto K (2006) Amadori-modified glycated albumin predominantly induces E-selectin expression on human umbilical vein endothelial cells through NADPH oxidase activation. Clin Chim Acta 367:137–143

    PubMed  CAS  Google Scholar 

  • Hovatta I, Tennant RS, Helton R, Marr RA, Singer O, Redwine JM, Ellison JA, Schadt EE, Verma IM, Lockhart DJ, Barlow C (2005) Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice. Nature 438:662–666

    PubMed  CAS  Google Scholar 

  • Hsieh PS, Huang WC (1993) Chemical sympathectomy attenuates hyperinsulinemia-induced hypertension in conscious rats. Nutr Metab Cardiovasc Dis 3:173–178

    Google Scholar 

  • Hudson BI, Carter AM, Harja E, Kalea AZ, Arriero M, Yang H, Grant PJ, Schmidt AM (2008) Identification, classification, and expression of RAGE gene splice variants. FASEB J 22:1572–1580

    PubMed  CAS  Google Scholar 

  • Iadecola C, Davisson RL (2008) Hypertension and cerebrovascular dysfunction. Cell Metab 7:476–484

    PubMed  CAS  Google Scholar 

  • Inoguchi T, Battan R, Handler E, Sportsman JR, Heath W, King GL (1992) Preferential elevation of protein kinase C isoform beta II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. Proc Natl Acad Sci USA 89:11059–11063

    PubMed  CAS  Google Scholar 

  • Jack MM, Ryals JM, Wright DE (2011) Characterisation of glyoxalase I in a streptozocin-induced mouse model of diabetes with painful and insensate neuropathy. Diabetologia 54:2174–2182

    PubMed  CAS  Google Scholar 

  • Jalal DI, Rivard CJ, Johnson RJ, Maahs DM, McFann K, Rewers M, Snell-Bergeon JK (2010) Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study. Nephrol Dial Transplant 25:1865–1869

    PubMed  CAS  Google Scholar 

  • Jalal DI, Maahs DM, Hovind P, Nakagawa T (2011) Uric acid as a mediator of diabetic nephropathy. Semin Nephrol 31:459–465

    PubMed  CAS  Google Scholar 

  • Jianghai L, Wang R, Desai K, Wu L (2012) Upregulation of aldolase B and overproduction of methylglyoxal in vascular tissues from rats with metabolic syndrome. Cardiovasc Res 92:494–503

    Google Scholar 

  • Johnson R, Kang D, Feig D, Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B, Herrera-Acosta J, Mazzali M (2003) Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 41:1183–1189

    PubMed  CAS  Google Scholar 

  • Juan CC, Fang VS, Hsu YP, Huang DB, Hsia DB, Yu PC, Kwok CF, Ho LT (1998) Overexpression of vascular endothelin-1 and endothelin-A receptors in a fructose-induced hypertensive rat model. J Hypertens 16:1775–1782

    PubMed  CAS  Google Scholar 

  • Kalousova M, Skrha J, Zima T (2002) Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res 51:597–604

    PubMed  CAS  Google Scholar 

  • Kalpouzos G, Eustache F, de la Sayette V, Viader F, Chetelat G, Desgranges B (2009a) Working memory and FDG-PET dissociate early and late onset alzheimer disease patients. J Neurol 252:548–558

    Google Scholar 

  • Kalpouzos G, Chetelat G, Baron JC, Landeau B, Mevel K, Godeau C, Barré L, Constans JM, Viader F, Eustache F, Desgranges B (2009b) Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging. Neurobiol Aging 30:112–124

    PubMed  CAS  Google Scholar 

  • Kanellis J, Feig D, Johnson R (2004) Does asymptomatic hyperuricaemia contribute to the development of renal and cardiovascular disease? An old controversy renewed. Nephrology (Carlton) 9:394–399

    Google Scholar 

  • Katakam PV, Ujhelyi MR, Hoenig ME, Miller AW (1998) Endothelial dysfunction precedes hypertension in diet-induced insulin resistance. Am J Physiol 275:R788–R792

    PubMed  CAS  Google Scholar 

  • Kawasaki T, Igarashi K, Koeda T, Sugimoto K, Nakagawa K, Hayashi S, Yamaji R, Inui H, Fukusato T, Yamanouchi T (2009) Rats fed fructose-enriched diets have characteristics of nonalcoholic hepatic steatosis. J Nutr 139:2067–2071

    PubMed  CAS  Google Scholar 

  • Kela U, Vijayvargiya R, Trivedi CP (1980) Inhibitory effects of methylxanthines on the activity of xanthine oxidase. Life Sci 27:2109–2119

    PubMed  CAS  Google Scholar 

  • Kelley D, Mitrakou A, Marsh H, Schwenk F, Benn J, Sonnenberg G, Arcangeli M, Aoki T, Sorensen J, Berger M (1988) Skeletal muscle glycolysis, oxidation, and storage of an oral glucose load. J Clin Invest 81:1563–1571

    PubMed  CAS  Google Scholar 

  • Khosla UM, Zharikov S, Finch JL, Nakagawa T, Roncal C, Mu W, Krotova K, Block ER, Prabhakar S, Johnson RJ (2005) Hyperuricemia induces endothelial dysfunction. Kidney Int 67:1739–1742

    PubMed  Google Scholar 

  • Kikuchi S, Shinpo K, Takeuchi M, Yamagishi S, Makita Z, Sasaki N, Tashiro K (2003) Glycation—a sweet tempter for neuronal death. Brain Res Brain Res Rev 41:306–323

    PubMed  CAS  Google Scholar 

  • Kim W, Hudson BI, Moser B, Guo J, Rong LL, Lu Y, Qu W, Lalla E, Lerner S, Chen Y, Yan SS, D’Agati V, Naka Y, Ramasamy R, Herold K, Yan SF, Schmidt AM (2005) Receptor for advanced glycation end products and its ligands: a journey from the complications of diabetes to its pathogenesis. Ann N Y Acad Sci 1043:553–561

    PubMed  CAS  Google Scholar 

  • Kim DS, Jeong SK, Kim HR, Kim DS, Chae SW, Chae HJ (2007) Effects of triglyceride on ER stress and insulin resistance. Biochem Biophys Res Commun 363:140–145

    PubMed  CAS  Google Scholar 

  • Kislinger T, Fu C, Huber B, Qu W, Taguchi A, Du Yan S, Hofmann M, Yan SF, Pischetsrieder M, Schmidt AM (1999) N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. J Biol Chem 274:31740–31749

    PubMed  CAS  Google Scholar 

  • Koo HY, Wallig MA, Chung BH, Nara TY, Cho BH, Nakamura MT (2008) Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver. Biochim Biophys Acta 1782:341–348

    PubMed  CAS  Google Scholar 

  • Kuhla B, Luth HJ, Haferburg D, Weick M, Reichenbach A, Arendt T, Münch G (2006) Pathological effects of glyoxalase I inhibition in SH-SY5Y neuroblastoma cells. J Neurosci Res 83:1591–1600

    PubMed  CAS  Google Scholar 

  • Lanaspa MA, Sanchez-Lozada LG, Cicerchi C, Li N, Roncal-Jimenez CA, Ishimoto T, Le M, Garcia GE, Thomas JB, Rivard CJ, Andres-Hernando A, Hunter B, Schreiner G, Rodriguez-Iturbe B, Sautin YY, Johnson RJ (2012) Uric acid stimulates fructokinase and accelerates fructose metabolism in the development of fatty liver. PLoS One 7:e47948

    PubMed  CAS  Google Scholar 

  • Lane MD, Cha SH (2009) Effect of glucose and fructose on food intake via malonyl-CoA signaling in the brain. Biochem Biophys Res Commun 382:1–5

    PubMed  CAS  Google Scholar 

  • Lane MD, Wolfgang M, Cha SH, Dai Y (2008) Regulation of food intake and energy expenditure by hypothalamic malonyl-CoA. Int J Obes (Lond) 32(Suppl 4):S49–S54

    CAS  Google Scholar 

  • Lee MY, Martin AS, Mehta PK, Dikalova AE, Garrido AM, Lyons E (2009) Mechanisms of vascular smooth muscle NADPH oxidase 1 (Nox1) contribution to injury-induced neointimal formation. Arterioscler Thromb Vasc Biol 29:103–110

    Google Scholar 

  • Lehninger A, Nelson D, Cox M (2005) Lehninger principles of biochemistry. W. H. Freeman, New York

    Google Scholar 

  • Levin BE, Kang L, Sanders NM, Dunn-Meynell AA (2006) Role of neuronal glucosensing in the regulation of energy homeostasis. Diabetes 55(Suppl 2):S122–S130

    CAS  Google Scholar 

  • Li JM, Li YC, Kong LD, Hu QH (2010) Curcumin inhibits hepatic protein-tyrosine phosphatase 1B and prevents hypertriglyceridemia and hepatic steatosis in fructose-fed rats. Hepatology 51:1555–1566

    PubMed  CAS  Google Scholar 

  • Locke GA, Cheng D, Witmer MR, Tamura JK, Haque T, Carney RF, Rendina AR, Marcinkeviciene J (2008) Differential activation of recombinant human acetyl-CoA carboxylases 1 and 2 by citrate. Arch Biochem Biophys 475:72–79

    PubMed  CAS  Google Scholar 

  • Lonardo A, Lombardini S, Ricchi M, Scaglioni F, Loria P (2005) Review article: hepatic steatosis and insulin resistance. Aliment Pharmacol Ther 22:64–70

    PubMed  CAS  Google Scholar 

  • Loos M, van der Sluis S, Bochdanovits Z, van Zutphen IJ, Pattij T, Stiedl O, Neuro-BSIK Mouse Phenomics consortium, Smit AB, Spijker S (2009) Activity and impulsive action are controlled by different genetic and environmental factors. Genes Brain Behav 8:817–828

    PubMed  CAS  Google Scholar 

  • Lue LF, Walker DG, Brachova L, Beach TG, Roger J, Schmidt AM, Stern DM, Yan SD (2001) Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer’s disease: identification of a cellular activation mechanism. Exp Neurol 171:29–45

    PubMed  CAS  Google Scholar 

  • Lukic IK, Humpert PM, Nawroth PP, Bierhaus A (2008) The RAGE pathway: activation and perpetuation in the pathogenesis of diabetic neuropathy. Ann N Y Acad Sci 1126:76–80

    PubMed  CAS  Google Scholar 

  • Lusis AJ, Attie AD, Reue K (2008) Metabolic syndrome: from epidemiology to systems biology. Nat Rev Genet 9:819–830

    PubMed  CAS  Google Scholar 

  • Madonna R, De Caterina R (2011) Cellular and molecular mechanisms of vascular injury in diabetes—Part II: cellular mechanisms and therapeutic targets. Vascul Pharmacol 54:75–79

    PubMed  CAS  Google Scholar 

  • Maenpaa PH, Raivio KO, Kekomaki MP (1968) Liver adenine nucleotides: fructose-induced depletion and its effect on protein synthesis. Science 161:1253–1254

    PubMed  CAS  Google Scholar 

  • Magnusson I, Rothman D, Katz L, Shulman R, Shulman G (1992) Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J Clin Invest 90:1323–1327

    PubMed  CAS  Google Scholar 

  • Mann GE, Yudilevich DL, Sobrevia L (2003) Regulation of amino acid and glucose transporters in endothelial and smooth muscle cells. Physiol Rev 83:183–252

    PubMed  CAS  Google Scholar 

  • Marshall RO, Kooi ER (1957) Enzymatic conversion of D-glucose to D-fructose. Science 125:648–649

    PubMed  CAS  Google Scholar 

  • Matsuzaka T, Shimano H, Yahagi N, Amemiya-Kudo M, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Tomita S, Sekiya M, Hasty A, Nakagawa Y, Sone H, Toyoshima H, Ishibashi S, Osuga J, Yamada N (2004) Insulin-independent induction of sterol regulatory element-binding protein-1c expression in the livers of streptozotocin-treated mice. Diabetes 53:560–569

    PubMed  CAS  Google Scholar 

  • McLellan AC, Thornalley PJ, Benn J, Sonksen PH (1994) Glyoxalase system in clinical diabetes mellitus and correlation with diabetic complications. Clin Sci (Lond) 87:21–29

    CAS  Google Scholar 

  • McPherson JD, Shilton BH, Walton DJ (1988) Role of fructose in glycation and cross-linking of proteins. Biochemistry 27:1901–1907

    PubMed  CAS  Google Scholar 

  • Meehan WP, Buchanan TA, Hsueh W (1994) Chronic insulin administration elevates blood pressure in rats. Hypertension 23:1012–1017

    PubMed  CAS  Google Scholar 

  • Méndez JD, Xie J, Aguilar-Hernández M, Méndez-Valenzuela V (2010) Trends in advanced glycation end products research in diabetes mellitus and its complications. Mol Cell Biochem 341:33–41

    PubMed  Google Scholar 

  • Meneghini V, Francese MT, Carraro L, Grilli M (2010) A novel role for the receptor for advanced glycation end-products in neural progenitor cells derived from adult subventricular zone. Mol Cell Neurosci 45:139–150

    PubMed  CAS  Google Scholar 

  • Messier C (2005) Impact of impaired glucose tolerance and type 2 diabetes on cognitive aging. Neurobiol Aging 26(Suppl 1):26–30

    PubMed  Google Scholar 

  • Miller CC, Martin RJ, Whitney ML, Edwards GL (2002) Intracerebroventricular injection of fructose stimulates feeding in rats. Nutr Neurosci 5:359–362

    PubMed  CAS  Google Scholar 

  • Moore MC, Davis SN, Mann SL, Cherrington AD (2001) Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes. Diabetes Care 24:1882–1887

    PubMed  CAS  Google Scholar 

  • Morgello S, Uson RR, Schwartz EJ, Haber RS (1995) The human blood-brain barrier glucose transporter (glut1) is a glucose transporter of gray matter astrocytes. Glia 14:43–54

    PubMed  CAS  Google Scholar 

  • Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI (2005) Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest 115:3587–3593

    PubMed  CAS  Google Scholar 

  • Morino K, Petersen KF, Shulman GL (2006) Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes 55(Suppl 2):S9–S15

    PubMed  CAS  Google Scholar 

  • Nakagawa T, Tuttle KR, Short RA, Johnson RJ (2005) Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol 1:80–86

    PubMed  CAS  Google Scholar 

  • Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, Ouyang X, Feig DI, Block ER, Herrera-Acosta J, Patel JM, Johnson RJ (2006) A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 290:F625–F631

    PubMed  CAS  Google Scholar 

  • Nalecz KA, Nalecz MJ (1996) Carnitine—a known compound, a novel function in neural cells. Acta Neurobiol Exp (Wars) 56:597–609

    CAS  Google Scholar 

  • Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A (1992) Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 267:14998–15004

    PubMed  CAS  Google Scholar 

  • Noland RC, Koves TR, Seiler SE, Lum H, Lust RM, Ilkayeva O, Stevens RD, Hegardt FG, Muoio DM (2009) Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control. J Biol Chem 284:22840–22852

    PubMed  CAS  Google Scholar 

  • Okada E, Oida K, Tada H, Asazuma K, Eguchi K, Tohda G, Kosaka S, Takahashi S, Miyamori I (1999) Hyperhomocysteinemia is a risk factor for coronary arteriosclerosis in Japanese patients with type 2 diabetes. Diabetes Care 22:484–490

    PubMed  CAS  Google Scholar 

  • Olofsson SO, Boren J (2005) Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis. J Intern Med 258:395–410

    PubMed  CAS  Google Scholar 

  • Oron-Herman M, Rosenthal T, Sela BA (2003) Hyperhomocysteinemia as a component of syndrome X. Metabolism 52:1491–1495

    PubMed  CAS  Google Scholar 

  • Ouyang X, Cirillo P, Sautin Y, McCall S, Bruchette JL, Diehl AM, Johnson RJ, Abdelmalek MF (2008) Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 48:993–999

    PubMed  CAS  Google Scholar 

  • Owen L, Sunram-Lea SI (2011) Metabolic agents that enhance ATP can improve cognitive functioning: a review of the evidence for glucose, oxygen, pyruvate, creatine, and L-carnitine. Nutrients 3:735–755

    PubMed  CAS  Google Scholar 

  • Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF Jr (1967) Brain metabolism during fasting. J Clin Invest 46:1589–1595

    PubMed  CAS  Google Scholar 

  • Panchal SK, Brown L (2011) Rodent models for metabolic syndrome research. J Biomed Biotechnol 2011:351982

    PubMed  Google Scholar 

  • Park CR (2001) Cognitive effects of insulin in the central nervous system. Neurosci Biobehav Rev 25:311–323

    PubMed  CAS  Google Scholar 

  • Parks EJ, Skokan LE, Timlin MT, Dingfelder CS (2008) Dietary sugars stimulate fatty acid synthesis in adults. J Nutr 138:1039–1046

    PubMed  CAS  Google Scholar 

  • Patel J, Iyer A, Brown L (2009) Evaluation of the chronic complications of diabetes in a high fructose diet in rats. Indian J Biochem Biophys 46:66–72

    PubMed  CAS  Google Scholar 

  • Petrie HJ, Chown SE, Belfie LM, Duncan AM, McLaren DH, Conquer JA, Graham TE (2004) Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss. Am J Clin Nutr 80:22–28

    PubMed  CAS  Google Scholar 

  • Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM (2005) Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15:16R–28R

    PubMed  CAS  Google Scholar 

  • Rayssiguier Y, Gueux E, Nowacki W, Rock E, Mazur A (2006) High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation. Magnes Res 19:237–243

    PubMed  CAS  Google Scholar 

  • Reger MA, Henderson ST, Hale C, Cholerton B, Baker LD, Watson GS, Hyde K, Chapman D, Craft S (2004) Effects of [beta]-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging 25:311–314

    PubMed  CAS  Google Scholar 

  • Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J (2004) Functional brain abnormalities in young adults at genetic risk for late-onset alzheimer’s dementia. Proc Natl Acad Sci USA 101:284–289

    PubMed  CAS  Google Scholar 

  • Roberts CK, Barnard RJ, Sindhu RK, Jurczak M, Ehdaie A, Vaziri ND (2006) Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome. Metabolism 55:928–934

    PubMed  CAS  Google Scholar 

  • Salomonsson I (2005) Shelf life: sucrose hydrolysis. Danisco Sugar A/S, 2005, Copenhagen, Denmark. www.danisco.com/cms/resources/file/eb241b041a6ed65/Shelf%20life.pdf. Accessed 15 Mar 2007

  • Samuel VT (2011) Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab 22:60–65

    PubMed  CAS  Google Scholar 

  • Samuel VT, Liu ZX, Wang A, Beddow SA, Geisler JG, Kahn M, Zhang X, Monia BP, Bhanot S, Shulman GI (2007) Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. J Clin Invest 117:739–745

    PubMed  CAS  Google Scholar 

  • Sasaki N, Toki S, Chowei H, Saito T, Nakano N, Hayashi Y, Takeuchi M, Makita Z (2001) Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer’s disease. Brain Res 888:256–262

    PubMed  CAS  Google Scholar 

  • Sautin YY, Nakagawa T, Zharikov S, Johnson RJ (2007) Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol 293:C584–C596

    PubMed  CAS  Google Scholar 

  • Sawa A, Khan AA, Hester LD, Snyder SH (1997) Glyceraldehyde-3-phosphate dehydrogenase: nuclear translocation participates in neuronal and nonneuronal cell death. Proc Natl Acad Sci USA 94:11669–11674

    PubMed  CAS  Google Scholar 

  • Schmidt AM, Hori O, Chen JX, Li JF, Crandall J, Zhang J, Cao R, Yan SD, Brett J, Stern D (1995) Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice: a potential mechanism for the accelerated vasculopathy of diabetes. J Clin Invest 96:1395–1403

    PubMed  CAS  Google Scholar 

  • Scivittaro V, Ganz MB, Weiss MF (2000) AGEs induce oxidative stress and activate protein kinase C-beta (II) in neonatal mesangial cells. Am J Physiol 278:F676–F683

    CAS  Google Scholar 

  • Seneff S, Wainwright G, Mascitelli L (2011) Is the metabolic syndrome caused by a high fructose, and relatively low fat, low cholesterol diet? Arch Med Sci 7:8–20

    PubMed  CAS  Google Scholar 

  • Shapiro A, Mu W, Roncal C, Cheng KY, Johnson RJ, Scarpace PJ (2008) Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Am J Physiol Regul Integr Comp Physiol 295:R1370–R1375

    PubMed  CAS  Google Scholar 

  • Shi Y, Galusha SA, Rock KL (2006) Cutting edge: elimination of an endogenous adjuvant reduces the activation of CD8 T lymphocytes to transplanted cells and in an autoimmune diabetes model. J Immunol 176:3905–3908

    PubMed  CAS  Google Scholar 

  • Shinohara M, Thornalley PJ, Giardino I, Beisswenger P, Thorpe SR, Onorato J, Brownlee M (1998) Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J Clin Invest 101:1142–1147

    PubMed  CAS  Google Scholar 

  • Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG (1990) Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 322:223–228

    PubMed  CAS  Google Scholar 

  • Sieber FE, Traystman RJ (1992) Special issues: glucose and the brain. Crit Care Med 20:104–114

    PubMed  CAS  Google Scholar 

  • Sieber FE, Derrer SA, Saudek CD, Traystman RJ (1989) Effect of hypoglycemia on cerebral metabolism and carbon dioxide responsivity. Am J Physiol 256:H697–H706

    PubMed  CAS  Google Scholar 

  • Singh R, Barden A, Mori T, Beilin L (2001) Advanced glycation end-products: a review. Diabetologia 44:129–146

    PubMed  CAS  Google Scholar 

  • Spanswick D, Smith MA, Mirshamsi S, Routh VH, Ashford ML (2000) Insulin activates ATP-sensitive K + channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci 3:757–758

    PubMed  CAS  Google Scholar 

  • Stanhope KL, Havel PJ (2008) Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Curr Opin Lipidol 19:16–24

    PubMed  CAS  Google Scholar 

  • Stanhope KL, Havel PJ (2009) Fructose consumption: considerations for future research on its effects on adipose distribution, lipid metabolism, and insulin sensitivity in humans. J Nutr 139:1236S–1241S

    PubMed  CAS  Google Scholar 

  • Stanhope KL, Griffen SC, Bair BR, Swarbrick MM, Keirn WL, Havel PJ (2008) Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. Am J Clin Nutr 87:1194–1203

    PubMed  CAS  Google Scholar 

  • Stavric B, Johnson WJ, Clayman S, Gadd RE, Chartrand A (1976) Effect of fructose administration on serum urate levels in the uricase inhibited rat. Experientia 32:373–374

    PubMed  CAS  Google Scholar 

  • Steiber A, Kerner J, Hoppel C (2004) Carnitine: a nutritional, biosynthetic, and functional perspective. Mol Aspects Med 25:455–473

    PubMed  CAS  Google Scholar 

  • Stirpe F, Della Corte E, Bonetti E, Abbondanza A, Abbati A, De Stefano F (1970) Fructose-induced hyperuricaemia. Lancet 2:1310–1311

    PubMed  CAS  Google Scholar 

  • Suárez G, Rajaram R, Oronsky AL, Gawinowicz MA (1989) Nonenzymatic glycation of bovine serum albumin by fructose (fructation). Comparison with the Maillard reaction initiated by glucose. J Biol Chem 264:3674–3679

    PubMed  Google Scholar 

  • Swarbrick MM, Stanhope KL, Elliott SS, Graham JL, Krauss RM, Christiansen MP, Griffen SC, Keim NL, Havel PJ (2008) Consumption of fructose-sweetened beverages for 10 weeks increases postprandial triacylglycerol and apolipoprotein-B concentrations in overweight and obese women. Br J Nutr 100:947–952

    PubMed  CAS  Google Scholar 

  • Tappy L (2012) Q&A: ‘toxic’ effects of sugar: should we be afraid of fructose? BMC Biol 10:42

    PubMed  CAS  Google Scholar 

  • Teff K, Elliot S, Tschoep MR (2002) Consuming high fructose meals reduces 24 hour plasma insulin and leptin concentrations, does not suppress circulating ghrelin, and increases postprandial and fasting triglycerides in women. Diabetes 52:A408

    Google Scholar 

  • Teff KL, Elliott SS, Tschop M, Kieffer TJ, Rader D, Heiman M, Townsend RR, Keim NL, D’Alessio D, Havel PJ (2004) Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab 89:2963–2972

    PubMed  CAS  Google Scholar 

  • Thorens B, Mueckler M (2010) Glucose transporters in the 21st Century. Am J Physiol Endocrinol Metab 298:E141–E145

    PubMed  CAS  Google Scholar 

  • Thornalley PJ (1993a) Modification of the glyoxalase system in disease processes and prospects for therapeutic strategies. Biochem Soc Trans 21:531–534

    PubMed  CAS  Google Scholar 

  • Thornalley PJ (1993b) The glyoxalase system in health and disease. Mol Aspects Med 14:287–371

    PubMed  CAS  Google Scholar 

  • Thornalley PJ (2003) Glyoxalase I—structure, function and a critical role in the enzymatic defence against glycation. Biochem Soc Trans 31:1343–1348

    PubMed  CAS  Google Scholar 

  • Tran LT, MacLeod KM, McNeill JH (2009) Chronic etanercept treatment prevents the development of hypertension in fructose-fed rats. Mol Cell Biochem 330:219–228

    PubMed  CAS  Google Scholar 

  • Unger JW, Moss AM, Livingston JN (1991) Immunohistochemical localization of insulin receptors and phosphotyrosine in the brainstem of the adult rat. Neuroscience 42:853–861

    PubMed  CAS  Google Scholar 

  • van den Berghe G, Bronfman M, Vanneste R, Hers HG (1977) The mechanism of adenosine triphosphate depletion in the liver after a load of fructose. A kinetic study of liver adenylate deaminase. Biochem J 162:601–609

    PubMed  Google Scholar 

  • Vannucci SJ (1994) Developmental expression of glut1 and glut3 glucose transporters in rat brain. J Neurochem 62:240–246

    PubMed  CAS  Google Scholar 

  • Vasdev S, Ford CA, Longerich L, Parai S, Gadag V, Wadhawan S (1998) Aldehyde induced hypertension in rats: prevention by N-acetyl cysteine. Artery 23:10–36

    PubMed  CAS  Google Scholar 

  • Vasdev S, Gill VD, Singal PK (2006) Modulation of oxidative stress-induced changes in hypertension and atherosclerosis by antioxidants. Exp Clin Cardiol 11:206–216

    PubMed  CAS  Google Scholar 

  • Verma S, Bhanot S, McNeill JH (1999) Sympathectomy prevents fructose-induced hyperinsulinemia and hypertension. Eur J Pharmacol 373:R1–R4

    PubMed  CAS  Google Scholar 

  • Vila L, Roglans N, Alegret M, Sanchez RM, Vazquez-Carrera M, Laguna JC (2008) Suppressor of cytokine signaling-3 (SOCS-3) and a deficit of serine/threonine (Ser/Thr) phosphoproteins involved in leptin transduction mediate the effect of fructose on rat liver lipid metabolism. Hepatology 48:1506–1516

    PubMed  CAS  Google Scholar 

  • Visinoni S, Fam BC, Blair A, Rantzau C, Lamont BJ, Bouwman R, Watt MJ, Proietto J, Favaloro JM, Andrikkopoulos S (2008) Increased glucose production in mice overexpressing human fructose-1,6-bisphosphatase in the liver. Am J Physiol Endocrinol Metab 295:E1132–E1141

    PubMed  CAS  Google Scholar 

  • Wang GJ, Volkow ND, Thanos PK, Fowler JS (2004) Similarity between obesity and drug addiction as assessed by neurofunctional imaging: a concept review. J Addict Dis 23:39–53

    PubMed  Google Scholar 

  • Wang X, Desai K, Chang T, Wu L (2005) Vascular methylglyoxal metabolism and the development of hypertension. J Hypertens 23:1565–1573

    PubMed  CAS  Google Scholar 

  • Wang X, Jia X, Chang T, Desai K, Wu L (2008) Attenuation of hypertension development by scavenging methylglyoxal in fructose-treated rats. J Hypertens 26:765–772

    PubMed  CAS  Google Scholar 

  • Watson GS, Craft S (2004) Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer’s disease. Eur J Pharmacol 490:97–113

    PubMed  CAS  Google Scholar 

  • Wautier JL, Guillausseau PJ (2001) Advanced glycation end products, their receptors and diabetic angiopathy. Diabetes Metab 27:535–542

    PubMed  CAS  Google Scholar 

  • Wautier JL, Schmidt AM (2004) Protein glycation: a firm link to endothelial cell dysfunction. Circ Res 95:233–238

    PubMed  CAS  Google Scholar 

  • Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM, Wautier JL (2001) Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab 280:E685–E694

    PubMed  CAS  Google Scholar 

  • Wolfgang MJ, Lane MD (2011) Hypothalamic malonyl-CoA and CPT1c in the treatment of obesity. FEBS J 278:552–558

    PubMed  CAS  Google Scholar 

  • Wolfgang MJ, Cha SH, Sidhaye A, Chohnan S, Cline G, Shulman GI, Lane MD (2007) Regulation of hypothalamic malonyl-CoA by central glucose and leptin. Proc Natl Acad Sci USA 104:19285–19290

    PubMed  CAS  Google Scholar 

  • Wu L (2006) Is methylglyoxal a causative factor for hypertension development? Can J Physiol Pharmacol 84:129–139

    PubMed  CAS  Google Scholar 

  • Wu T, Willett WC, Hankinson SE, Giovannucci E (2005) Caffeinated coffee, decaffeinated coffee, and caffeine in relation to plasma C-peptide levels, a marker of insulin secretion, in U.S. women. Diabetes Care 28:1390–1396

    PubMed  CAS  Google Scholar 

  • Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF, Achong MK (1998) IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 101:311–320

    PubMed  CAS  Google Scholar 

  • Yan SD, Schmidt AM, Anderson GM, Zhang J, Brett J, Zou YS, Pinsky D, Stern D (1994) Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem 269:9889–9897

    PubMed  CAS  Google Scholar 

  • Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, Slattery T, Zhao L, Nagashima M, Moser J, Migheli A, Nawroth P, Stern D, Schmidt AM (1996) RAGE and amyloid-β peptide neurotoxicity in Alzheimer’s disease. Nature 382:685–691

    PubMed  CAS  Google Scholar 

  • Yoo HG, Lee SI, Chae HJ, Park SJ, Lee YC, Yoo WH (2009) Prevalence of insulin resistance and metabolic syndrome in patients with gouty arthritis. Rheumatol Int 20:231–235

    Google Scholar 

  • Zimmermann R, Panzenböck U, Wintersperger A, Levak-Frank S, Graier W, Glatter O, Fritz G, Kostner GM, Zechner R (2001) Lipoprotein lipase mediates the uptake of glycated LDL in fibroblasts, endothelial cells, and macrophages. Diabetes 50:1643–1653

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ohio State University, Columbus, OH, USA

    Akhlaq A. Farooqui

Authors
  1. Akhlaq A. Farooqui
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Farooqui, A.A. (2013). Glucose- and Fructose-Induced Toxicity in the Liver and Brain. In: Metabolic Syndrome. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7318-3_2

Download citation

Publish with us

Policies and ethics

Search

Navigation