Molecular and Cellular Biochemistry

, Volume 261, Issue 1, pp 23–33 | Cite as

Fructose transport and metabolism in adipose tissue of Zucker rats: Diminished GLUT5 activity during obesity and insulin resistance

  • Gary J. Litherland
  • Eric Hajduch
  • Gwyn W. Gould
  • Harinder S. Hundal
Article

Abstract

Fructose is a major dietary sugar, which is elevated in the serum of diabetic humans, and is associated with metabolic syndromes important in the pathogenesis of diabetic complications. The facilitative fructose transporter, GLUT5, is expressed in insulin-sensitive tissues (skeletal muscle and adipocytes) of humans and rodents, where it mediates the uptake of substantial quantities of dietary fructose, but little is known about its regulation. We found that GLUT5 abundance and activity were compromised severely during obesity and insulin resistance in Zucker rat adipocytes. Adipocytes from young obese (fa/fa), highly insulin-responsive Zucker rats contained considerably more plasma membrane GLUT5 than those from their lean counterparts (1.8-fold per microgram membrane protein), and consequently exhibited higher fructose transport (fivefold) and metabolism (threefold) rates. Lactate production was the preferred route for fructose metabolism in these cells. As the rats aged and become more obese and insulin-resistant, adipocyte GLUT5 surface density (12-fold) and fructose transport (10-fold) and utilisation rates (threefold) fell markedly. The GLUT5 loss was more dramatic in adipocytes from obese animals, which developed a more marked insulin resistance than lean counterparts. The decline of GLUT5 levels in adipocytes from older, obese animals was not a generalised effect, and was not observed in kidney, nor was this expression pattern shared by the α1 subunit of the Na+/K+ ATPase. Our findings suggest that plasma membrane GLUT5 levels and thus fructose utilisation rates in adipocytes are dependent upon cellular insulin sensitivity, inferring a possible role for GLUT5 in the elevated circulating fructose observed during diabetes, and associated pathological complications. (Mol Cell Biochem 261: 23–33, 2004)

GLUT4 glucose membrane muscle diabetes 

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References

  1. 1.
    Thorburn AW, Storlien LH, Jenkins AB, Khouri S, Kraegen EW: Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats. Am J Clin Nutr 49: 1155–1163, 1989PubMedGoogle Scholar
  2. 2.
    McPherson JD, Shilton BH, Walton DJ: Role of fructose in glycation and cross-linking of proteins. Biochemistry 27: 1901–1907, 1988CrossRefPubMedGoogle Scholar
  3. 3.
    Kawasaki T, Akanuma H, Yamanouchi T: Increased fructose concentrations in blood and urine in patients with diabetes. Diabetes Care 25: 353–357, 2002PubMedGoogle Scholar
  4. 4.
    Davidson NO, Hausman AM, Ifkovits CA, Buse JB, Gould GW, Burant CF, Bell GI: Human intestinal glucose transporter expression and localization of GLUT5. Am J Physiol 262: C795–C800, 1992PubMedGoogle Scholar
  5. 5.
    Cheeseman CI: GLUT2 is the transporter for fructose across the rat intestinal basolateral membrane. Gastroenterology 105: 1050–1056, 1993PubMedGoogle Scholar
  6. 6.
    Colville CA, Seatter MJ, Jess TJ, Gould GW, Thomas HM: Kinetic analysis of the liver-type (GLUT2) and brain-type (GLUT3) glucose transporters in Xenopus oocytes: Substrate specificities and effects of transport inhibitors. Biochem J 290: 701–706, 1993PubMedGoogle Scholar
  7. 11.
    Froesch ER, Ginsberg JL: Fructose metabolism of adipose tissue. Comparison of fructose and glucose metabolism in epididymal adipose tissue of normal rats. J Biol Chem 237: 3317–3324, 1962PubMedGoogle Scholar
  8. 12.
    Mayes PA: Intermediary metabolism of fructose. Am J Clin Nutr 58: 754S–765S, 1993PubMedGoogle Scholar
  9. 13.
    Inukai K, Asano T, Katagiri H, Ishihara H, Anai M, Fukushima Y, Tsukuda K, Kikuchi M, Yazaki Y, Oka Y: Cloning and increased expression with fructose feeding of rat jejunal GLUT5. Endocrinology 133: 2009–2014, 1993CrossRefPubMedGoogle Scholar
  10. 14.
    Burant CF, Saxena M: Rapid reversible substrate regulation of fructose transporter expression in rat small intestine and kidney. Am J Physiol 267: G71–G79, 1994PubMedGoogle Scholar
  11. 15.
    Mesonero J, Matosin M, Cambier D, Rodriguez-Yoldi MJ, Brot-Laroche E: Sugar-dependent expression of the fructose transporter GLUT5 in Caco-2 cells. Biochem J 312: 757–762, 1995PubMedGoogle Scholar
  12. 16.
    Matosin-Matekalo M, Mesonero JE, Laroche TJ, Lacasa M, Brot-Laroche E: Glucose and thyroid hormone co-regulate the expression of the intestinal fructose transporter GLUT5. Biochem J 339: 233–239, 1999CrossRefPubMedGoogle Scholar
  13. 17.
    Shah SW, Zhao H, Low SY, Mcardle HJ, Hundal HS: Characterization of glucose transport and glucose transporters in the human choriocarcinoma cell line, BeWo. Placenta 20: 651–659, 1999CrossRefPubMedGoogle Scholar
  14. 18.
    Hajduch E, Aledo JC, Watts C, Hundal HS: Proteolytic cleavage of cellubrevin and vesicle-associated membrane protein (VAMP) by tetanus toxin does not impair insulin-stimulated glucose transport or GLUT4 translocation in rat adipocytes. Biochem J 321: 233–238, 1997PubMedGoogle Scholar
  15. 19.
    Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254, 1976CrossRefPubMedGoogle Scholar
  16. 20.
    Hajduch EJ, Guerre-Millo MC, Hainault IA, Guichard CM, Lavau MM: Expression of glucose transporters (GLUT 1 and GLUT 4) in primary cultured rat adipocytes: Differential evolution with time and chronic insulin effect. J Cell Biochem 49: 251–258, 1992CrossRefPubMedGoogle Scholar
  17. 21.
    Schagger H, Jagow G: Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem 166: 368–379, 1987CrossRefPubMedGoogle Scholar
  18. 22.
    Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685, 1970CrossRefPubMedGoogle Scholar
  19. 23.
    Guerre-Millo M, Lavau M, Horne JS, Wardzala LJ: Proposed mechanism for increased insulin-mediated glucose transport in adipose cells from young, obese Zucker rats. Large intracellular pool of glucose transporters. J Biol Chem 260: 2197–2201, 1985PubMedGoogle Scholar
  20. 24.
    Pedersen O, Kahn CR, Kahn BB: Divergent regulation of the Glut 1 and Glut 4 glucose transporters in isolated adipocytes from Zucker rats. J Clin Invest 89: 1964–1973, 1992PubMedGoogle Scholar
  21. 25.
    Hainault I, Guerre-Millo M, Guichard C, Lavau M: Differential regulation of adipose tissue glucose transporters in genetic obesity (fatty rat). Selective increase in the adipose cell/muscle glucose transporter (GLUT 4) expression. J Clin Invest 87: 1127–1131, 1991PubMedGoogle Scholar
  22. 26.
    Urayama O, Shutt H, Sweadner KJ: Identification of three isozyme proteins of the catalytic subunit of the Na,K-ATPase in rat brain. J Biol Chem 264: 8271–8280, 1989PubMedGoogle Scholar
  23. 27.
    Johnson PR, Stern JS, Greenwood MR, Hirsch J: Adipose tissue hyperplasia and hyperinsulinemia on Zucker obese female rats: A developmental study. Metabolism 27: 1941–1954, 1978PubMedGoogle Scholar
  24. 28.
    Dani C, Bertrand B, Bardon S, Doglio A, Amri E, Grimaldi P: Regulation of gene expression by insulin in adipose cells: Opposite effects on adipsin and glycerophosphate dehydrogenase genes. Mol Cell Endocrinol 63: 199–208, 1989CrossRefPubMedGoogle Scholar
  25. 29.
    Pratley RE, Ren K, Milner MR, Sell SM: Insulin increases leptin mRNA expression in abdominal subcutaneous adipose tissue in humans. Mol Genet Metab 70: 19–26, 2000CrossRefPubMedGoogle Scholar
  26. 30.
    Ducluzeau PH, Perretti N, Laville M, Andreelli F, Vega N, Riou JP, Vidal H: Regulation by insulin of gene expression in human skeletal muscle and adipose tissue. Evidence for specific defects in type 2 diabetes. Diabetes 50: 1134–1142, 2001PubMedGoogle Scholar
  27. 31.
    Corpe C, Sreenan S, Burant C: Effects of type-2 diabetes and troglitazone on the expression patterns of small intestinal sugar transporters and ppar-gamma in the zucker diabetic fatty rat. Digestion 63: 116–123, 1901Google Scholar
  28. 32.
    Ibrahimi A, Teboul L, Gaillard D, Amri EZ, Ailhaud G, Young P, Cawthorne MA, Grimaldi PA: Evidence for a common mechanism of action for fatty acids and thiazolidinedione antidiabetic agents on gene expression in preadipose cells. Mol Pharmacol 46: 1070–1076, 1994PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Gary J. Litherland
    • 1
  • Eric Hajduch
    • 1
  • Gwyn W. Gould
    • 2
  • Harinder S. Hundal
    • 1
  1. 1.Division of Molecular Physiology, School of Life Sciences, Medical Sciences Institute/Wellcome Trust Biocentre ComplexThe University of DundeeDundeeUK
  2. 2.Division of Biochemistry and Molecular BiologyUniversity of GlasgowGlasgowUK

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