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Chemical Compound Review

Phlorizin     1-[2,4-dihydroxy-6- [(2S,3R,4S,5S,6R)-3,4,5...

Synonyms: Floridzin, Phlorhizin, Phloridzin, Phlorizine, Phlorrhizen, ...
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Disease relevance of Phloridzin

  • This effect cannot be attributed to the correction of hyperglycemia because phlorizin therapy had no direct influence on the glycogenic pathway [1].
  • In normal dogs made hyperglucagonemic by phloridzin pretreatment, insulin and somatostatin suppressed glucagon at rates of 47 +/- 8 and 35 +/- 8%/h (NS), respectively, despite profound hypoglycemia [2].
  • Ischemia did, however, reduce the BBM sphingomyelin-to-phosphatidylcholine (SPH/PC) and cholesterol-to-phospholipid ratios and the number of specific high-affinity Na+-dependent phlorizin binding sites (390 +/- 43 vs. 146 +/- 24 pmol/mg; P less than 0.01) without altering the binding dissociation constant (Kd) [3].
  • Phlorizin treatment prevented hyperglycemia (61 +/- 2 vs. 145 +/- 7 mg/dl, treated versus nontreated; P < 0.0001) and lowered islet TAG content (32.7 +/- 0.7 vs. 47.8 +/- 2.7 ng/islet, treated versus nontreated; P < 0.0001) and preserved insulin mRNA levels without preventing hypertriglyceridemia [4].
  • Association of these changes with beta cell hypertrophy, increased mRNA levels of the transcription factor c-Myc, and their complete normalization by phlorizin treatment suggested a link between chronic hyperglycemia, increased c-Myc expression, and altered beta cell function [5].

Psychiatry related information on Phloridzin


High impact information on Phloridzin

  • To investigate the mechanisms of this abnormality, we measured glucose transport Vmax, the total transporter number, their average intrinsic activity, GLUT4 and GLUT1 contents in skeletal muscle plasma membrane vesicles from basal or insulin-stimulated streptozocin diabetic rats with different duration of diabetes, treated or not with phlorizin [7].
  • Normalization of circulating glucose in the rat model by either insulin or phlorizin treatment did not result in a reduction in membrane PKC isozyme protein or kinase activity [8].
  • Euglycemic (approximately 7 mM) insulin (approximately 2,500 pM) clamps with saline or GlcN infusions were performed in control (CON; plasma glucose [PG] = 7.4 +/- 0.2 mM), diabetic (D; PG = 19.7 +/- 1.1), and phlorizin-treated (3-wk) diabetic rats (D + PHL; PG = 7.6 +/- 0.9) [9].
  • Levels of the HepG2/brain GT protein and mRNA are unaltered by diabetes or phlorizin treatment [10].
  • These results suggest that (a) the defect in muscle glycogen synthesis is the major determinant of insulin resistance in diabetic rats; (b) both vanadate and phlorizin treatment normalize meal tolerance and insulin sensitivity in diabetic rats; (c) vanadate treatment specifically reverses the defect in muscle glycogen synthesis in diabetic rats [1].

Chemical compound and disease context of Phloridzin


Biological context of Phloridzin

  • This postnatal increase in Vmax was paralleled by a similar increase in the number of phlorizin binding sites [15].
  • To define the role of hyperglycemia in generation of the insulin resistance, we examined the effect of phlorizin treatment on tissue sensitivity to insulin in partially pancreatectomized rats [16].
  • This study provides the first evidence that rat LPH has its major catalytic site at E1750, representing all of the lactase and the majority of the phlorizin hydrolase activity [17].
  • Specific blockage of the phlorizin hydrolase site of LPH using 2',4'-dintrophenyl-2-fluoro-2-deoxy-beta-D-glucopyranoside did not reduce PNG hydrolysis [18].
  • The expressed transport activity was 96% Na(+)-dependent, saturable (apparent Km = 15 microM) and inhibited by phloridzin (IC50 = 100 microM) [19].

Anatomical context of Phloridzin

  • This is consistent with earlier studies on phlorizin binding to the brush border membrane of duodenal biopsy specimens from this patient [20].
  • Accumulation of D-glucose within the enterocytes was decreased significantly by 67% and 79% when acarbose (1 mg/mL) or phloridzin (2 mmol/L), respectively, were present in the luminal perfusate [21].
  • Radioautography revealed that, in chronic diabetes, specific phlorizin binding extends into the midvillus region of the ileum, whereas in age-matched controls, it is confined to villus tips [22].
  • Glucose uptake into isolated vacuoles was inhibited by NH(4)(+), fructose, and phlorizin, indicating that transport is energy-dependent and that both glucose and fructose were taken up by the same carrier [23].
  • In one of these, the human carcinoma cell line T84, phlorizin inhibitable uptake of beta-D-Glc-IPM was demonstrated with substrate saturation and an apparent Km of 0.4 mM [24].

Associations of Phloridzin with other chemical compounds


Gene context of Phloridzin


Analytical, diagnostic and therapeutic context of Phloridzin


  1. Correction of chronic hyperglycemia with vanadate, but not with phlorizin, normalizes in vivo glycogen repletion and in vitro glycogen synthase activity in diabetic skeletal muscle. Rossetti, L., Lauglin, M.R. J. Clin. Invest. (1989) [Pubmed]
  2. Relationship of glucagon suppression by insulin and somatostatin to the ambient glucose concentration. Starke, A., Imamura, T., Unger, R.H. J. Clin. Invest. (1987) [Pubmed]
  3. Ischemia induces surface membrane dysfunction. Mechanism of altered Na+-dependent glucose transport. Molitoris, B.A., Kinne, R. J. Clin. Invest. (1987) [Pubmed]
  4. Antecedent hyperglycemia, not hyperlipidemia, is associated with increased islet triacylglycerol content and decreased insulin gene mRNA level in Zucker diabetic fatty rats. Harmon, J.S., Gleason, C.E., Tanaka, Y., Poitout, V., Robertson, R.P. Diabetes (2001) [Pubmed]
  5. High glucose stimulates early response gene c-Myc expression in rat pancreatic beta cells. Jonas, J.C., Laybutt, D.R., Steil, G.M., Trivedi, N., Pertusa, J.G., Van de Casteele, M., Weir, G.C., Henquin, J.C. J. Biol. Chem. (2001) [Pubmed]
  6. Phlorizin administration does not attenuate hypophagia induced by intraruminal propionate infusion in lactating dairy cattle. Bradford, B.J., Allen, M.S. J. Nutr. (2007) [Pubmed]
  7. Mechanisms and time course of impaired skeletal muscle glucose transport activity in streptozocin diabetic rats. Napoli, R., Hirshman, M.F., Horton, E.S. J. Clin. Invest. (1995) [Pubmed]
  8. Protein kinase C is increased in the liver of humans and rats with non-insulin-dependent diabetes mellitus: an alteration not due to hyperglycemia. Considine, R.V., Nyce, M.R., Allen, L.E., Morales, L.M., Triester, S., Serrano, J., Colberg, J., Lanza-Jacoby, S., Caro, J.F. J. Clin. Invest. (1995) [Pubmed]
  9. In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats. Rossetti, L., Hawkins, M., Chen, W., Gindi, J., Barzilai, N. J. Clin. Invest. (1995) [Pubmed]
  10. Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression. Kahn, B.B., Shulman, G.I., DeFronzo, R.A., Cushman, S.W., Rossetti, L. J. Clin. Invest. (1991) [Pubmed]
  11. Correction of hyperglycemia with phloridzin restores the glucagon response to glucose in insulin-deficient dogs: implications for human diabetes. Starke, A., Grundy, S., McGarry, J.D., Unger, R.H. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  12. Phlorizin treatment of diabetic rats partially reverses the abnormal expression of genes involved in hepatic glucose metabolism. Brichard, S.M., Henquin, J.C., Girard, J. Diabetologia (1993) [Pubmed]
  13. Effect of in vivo vanadate treatment on insulin receptor tyrosine kinase activity in partially pancreatectomized diabetic rats. Cordera, R., Andraghetti, G., DeFronzo, R.A., Rossetti, L. Endocrinology (1990) [Pubmed]
  14. Studies on the depression of gamma-aminobutyric acid potentials by phloridzin in cat dorsal root ganglion cells in vitro. Stevens, D.R., Gallagher, J.P., Shinnick-Gallagher, P. Neurosci. Lett. (1985) [Pubmed]
  15. Characterization of the fetal glucose transporter in rabbit kidney. Comparison with the adult brush border electrogenic Na+-glucose symporter. Beck, J.C., Lipkowitz, M.S., Abramson, R.G. J. Clin. Invest. (1988) [Pubmed]
  16. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. Rossetti, L., Smith, D., Shulman, G.I., Papachristou, D., DeFronzo, R.A. J. Clin. Invest. (1987) [Pubmed]
  17. Verification of the lactase site of rat lactase-phlorizin hydrolase by site-directed mutagenesis. Neele, A.M., Einerhand, A.W., Dekker, J., Büller, H.A., Freund, J.N., Verhave, M., Grand, R.J., Montgomery, R.K. Gastroenterology (1995) [Pubmed]
  18. Enzymatic hydrolysis of pyridoxine-5'-beta-D-glucoside is catalyzed by intestinal lactase-phlorizin hydrolase. Mackey, A.D., Henderson, G.N., Gregory, J.F. J. Biol. Chem. (2002) [Pubmed]
  19. Functional expression of Na(+)-dependent nucleoside transport systems of rat intestine in isolated oocytes of Xenopus laevis. Demonstration that rat jejunum expresses the purine-selective system N1 (cif) and a second, novel system N3 having broad specificity for purine and pyrimidine nucleosides. Huang, Q.Q., Harvey, C.M., Paterson, A.R., Cass, C.E., Young, J.D. J. Biol. Chem. (1993) [Pubmed]
  20. Compound missense mutations in the sodium/D-glucose cotransporter result in trafficking defects. Martín, M.G., Lostao, M.P., Turk, E., Lam, J., Kreman, M., Wright, E.M. Gastroenterology (1997) [Pubmed]
  21. Inhibition of glucose absorption in the rat jejunum: a novel action of alpha-D-glucosidase inhibitors. Hirsh, A.J., Yao, S.Y., Young, J.D., Cheeseman, C.I. Gastroenterology (1997) [Pubmed]
  22. Induction of intestinal glucose carriers in streptozocin-treated chronically diabetic rats. Fedorak, R.N., Gershon, M.D., Field, M. Gastroenterology (1989) [Pubmed]
  23. Molecular identification and physiological characterization of a novel monosaccharide transporter from Arabidopsis involved in vacuolar sugar transport. Wormit, A., Trentmann, O., Feifer, I., Lohr, C., Tjaden, J., Meyer, S., Schmidt, U., Martinoia, E., Neuhaus, H.E. Plant Cell (2006) [Pubmed]
  24. Transport of the new chemotherapeutic agent beta-D-glucosylisophosphoramide mustard (D-19575) into tumor cells is mediated by the Na+-D-glucose cotransporter SAAT1. Veyhl, M., Wagner, K., Volk, C., Gorboulev, V., Baumgarten, K., Weber, W.M., Schaper, M., Bertram, B., Wiessler, M., Koepsell, H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  25. Expression of size-selected mRNA encoding the intestinal Na/glucose cotransporter in Xenopus laevis oocytes. Hediger, M.A., Ikeda, T., Coady, M., Gundersen, C.B., Wright, E.M. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  26. Cyclosporin binding to a protein component of the renal Na(+)-D-glucose cotransporter. Ziegler, K., Frimmer, M., Fritzsch, G., Koepsell, H. J. Biol. Chem. (1990) [Pubmed]
  27. High affinity phlorizin binding to the LLC-PK1 cells exhibits a sodium:phlorizin stoichiometry of 2:1. Moran, A., Davis, L.J., Turner, R.J. J. Biol. Chem. (1988) [Pubmed]
  28. Cytochrome P450 1A1 expression and activity in Caco-2 cells: modulation by apple juice extract and certain apple polyphenols. Pohl, C., Will, F., Dietrich, H., Schrenk, D. J. Agric. Food Chem. (2006) [Pubmed]
  29. Insulin deficiency downregulated heat shock protein 60 and IGF-1 receptor signaling in diabetic myocardium. Chen, H.S., Shan, Y.X., Yang, T.L., Lin, H.D., Chen, J.W., Lin, S.J., Wang, P.H. Diabetes (2005) [Pubmed]
  30. High-yield functional expression of human sodium/d-glucose cotransporter1 in Pichia pastoris and characterization of ligand-induced conformational changes as studied by tryptophan fluorescence. Tyagi, N.K., Goyal, P., Kumar, A., Pandey, D., Siess, W., Kinne, R.K. Biochemistry (2005) [Pubmed]
  31. Absorption of quercetin-3-glucoside and quercetin-4'-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter. Day, A.J., Gee, J.M., DuPont, M.S., Johnson, I.T., Williamson, G. Biochem. Pharmacol. (2003) [Pubmed]
  32. The lactase phlorizin hydrolase (LCT) gene maps to pig chromosome 15q13. Thomsen, P.D., Johansson, M., Troelsen, J.T., Andersson, L. Anim. Genet. (1995) [Pubmed]
  33. Evidence for glucose/hexosamine in vivo regulation of insulin/IGF-I hybrid receptor assembly. Federici, M., Giaccari, A., Hribal, M.L., Giovannone, B., Lauro, D., Morviducci, L., Pastore, L., Tamburrano, G., Lauro, R., Sesti, G. Diabetes (1999) [Pubmed]
  34. Plasmodial surface anion channel-independent phloridzin resistance in Plasmodium falciparum. Desai, S.A., Alkhalil, A., Kang, M., Ashfaq, U., Nguyen, M.L. J. Biol. Chem. (2005) [Pubmed]
  35. T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Oku, A., Ueta, K., Arakawa, K., Ishihara, T., Nawano, M., Kuronuma, Y., Matsumoto, M., Saito, A., Tsujihara, K., Anai, M., Asano, T., Kanai, Y., Endou, H. Diabetes (1999) [Pubmed]
  36. In vivo and in vitro regulation of hepatic glucagon receptor mRNA concentration by glucose metabolism. Burcelin, R., Mrejen, C., Decaux, J.F., De Mouzon, S.H., Girard, J., Charron, M.J. J. Biol. Chem. (1998) [Pubmed]
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