Journal of Natural Medicines

, Volume 65, Issue 1, pp 50–56

Ginkgo biloba extract enhances glucose tolerance in hyperinsulinism-induced hepatic cells

Original Paper


Ginkgo biloba, an herbal medication, is capable of lowering glucose, fat, and lipid peroxide in diabetic patients. In the current study, we tested the hypothesis that Ginkgo biloba extract (GBE) prevented hyperinsulinism-induced glucose intolerance in hepatocytes. We investigated the effects of GBE on glucose consumption, glucokinase activity, and mRNA levels of key genes in glucose metabolism and the insulin signaling pathway. To better show its efficacy, we included a control group that was treated with rosiglitazone, a type of thiazolidinedione (TZD). The data indicated that GBE repressed glucose uptake under normal conditions, while it dramatically improved glucose tolerance under insulin-resistant conditions. Furthermore, after analyzing gene expression, we suggest that GBE chiefly exerts its effects by stimulating IRS-2 transcription. It should be noted that, unlike rosiglitazone, GBE did not stimulate excessive glucose uptake as it improved glucose tolerance. It is said that GBE treatment could avoid drug-induced obesity. Our data suggest that GBE has the potential to prevent insulin resistance and is a promising anti-diabetic drug.


Herb Thiazolidinedione Diabetes Insulin resistance Hepatocytes 



Ginkgo biloba extract




Insulin receptor substrate


Glucose transporter


Peroxisome proliferator-activated receptor


Sterol regulatory element-binding protein




  1. 1.
    Della Loggia R, Sosa S, Tubaro A, Morazzoni P, Bombardelli E, Griffini A (1996) Anti-inflammatory activity of some Ginkgo biloba constituents and of their phospholipid-complexes. Fitoterapia 67:257–264Google Scholar
  2. 2.
    Omar ME, Baiuomy AR, El-Batran S, Arbid MS (2004) Evaluation of the anti-inflammatory, anti-nociceptive and gastric effects of Ginkgo biloba in the rat. Pharmacol Res 49:133–142CrossRefGoogle Scholar
  3. 3.
    Bombardelli E, Cristoni A, Curri SB (1996) Activity of phospholipid-complex of Ginkgo biloba dimeric flavonoids on the skin microcirculation. Fitoterapia 67:265–273Google Scholar
  4. 4.
    Saponara R, Bosisio E (1998) Inhibition of cAMP-phosphodiesterase by biflavones of Ginkgo biloba in rat adipose tissue. J Nat Prod 61:1386–1387PubMedCrossRefGoogle Scholar
  5. 5.
    Dell’Agli M, Bosisio E (2002) Biflavones of Ginkgo biloba stimulate lipolysis in 3T3-L1 adipocytes. Planta Med 68:76–79PubMedCrossRefGoogle Scholar
  6. 6.
    Boveris AD, Galatro A, Puntarulo S (2000) Effect of nitric oxide and plant antioxidants on microsomal content of lipid radicals. Biol Res 33:159–165PubMedCrossRefGoogle Scholar
  7. 7.
    Nian H, Song B, Wang W (2004) Antioxidative stress effect of Ginkgo biloba extract to experimental diabetes rats. J Mudanjiang Med Coll 25:3–6Google Scholar
  8. 8.
    Wei Z, Peng Q, Lau BH, Shah V (1999) Ginkgo biloba inhibits hydrogen peroxide-induced activation of nuclear factor kappa B in vascular endothelial cells. Gen Pharmacol 33:369–375PubMedCrossRefGoogle Scholar
  9. 9.
    Maitra I, Marcocci L, Droy-Lefaix MT, Packer L (1995) Peroxyl radical scavenging activity of Ginkgo biloba extract EGb 761. Biochem Pharmacol 49:1649–1655PubMedCrossRefGoogle Scholar
  10. 10.
    Bernardczyk-Meller J, Siwiec-Proscinska J, Stankiewicz W, Fichna P, Pecold K, Korman E (2004) Influence of Eqb 761 on the function of the retina in children and adolescent with long lasting diabetes mellitus––preliminary report. Klin Oczna 106:569–571PubMedGoogle Scholar
  11. 11.
    Bell GI, Kayano T, Buse JB, Burant CF, Takeda J, Lin D, Fukumoto H, Seino S (1990) Molecular biology of mammalian glucose transporters. Diabetes Care 13:198–208PubMedCrossRefGoogle Scholar
  12. 12.
    Memon RA, Tecott LH, Nonogaki K, Beigneux A, Moser AH, Grunfeld C, Feingold KR (2000) Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice. Endocrinology 141:4021–4031PubMedCrossRefGoogle Scholar
  13. 13.
    Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109:1125–1131PubMedGoogle Scholar
  14. 14.
    Patti ME, Sun XJ, Bruening JC, Araki E, Lipes MA, White MF, Kahn CR (1995) 4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice. J Biol Chem 270:24670–24673PubMedCrossRefGoogle Scholar
  15. 15.
    Rother KI, Imai Y, Caruso M, Beguinot F, Formisano P, Accili D (1998) Evidence that IRS-2 phosphorylation is required for insulin action in hepatocytes. J Biol Chem 273:17491–17497PubMedCrossRefGoogle Scholar
  16. 16.
    Yeh H, Chu T, Shen T (1980) Ultrastructure of continuously cultured adult human liver cell. Acta Biol Exp Sin 13:361–364Google Scholar
  17. 17.
    Li C, Ning G, Chen J (1999) Establishing and identifying insulin-resistant HepG2 cell line. Chin J Diabetes 7:198–200Google Scholar
  18. 18.
    Garvey WT, Olefsky JM, Marshall S (1985) Insulin receptor down-regulation is linked to an insulin-induced postreceptor defect in the glucose transport system in rat adipocytes. J Clin Invest 76:22–30PubMedCrossRefGoogle Scholar
  19. 19.
    Pryor PR, Liu SC, Clark AE, Yang J, Holman GD, Tosh D (2000) Chronic insulin effects on insulin signalling and GLUT4 endocytosis are reversed by metformin. Biochem J 348 Pt 1:83–91PubMedCrossRefGoogle Scholar
  20. 20.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedCrossRefGoogle Scholar
  21. 21.
    Fernandez-Mejia C, Vega-Allende J, Rojas-Ochoa A, Rodriguez-Dorantes M, Romero-Navarro G, Matschinsky FM, Wang J, German MS (2001) Cyclic adenosine 3′,5′-monophosphate increases pancreatic glucokinase activity and gene expression. Endocrinology 142:1448–1452PubMedCrossRefGoogle Scholar
  22. 22.
    Yki-Jarvinen H (2004) Thiazolidinediones. N Engl J Med 351:1106–1118PubMedCrossRefGoogle Scholar
  23. 23.
    Miyazaki Y, He H, Mandarino LJ, DeFronzo RA (2003) Rosiglitazone improves downstream insulin receptor signaling in type 2 diabetic patients. Diabetes 52:1943–1950PubMedCrossRefGoogle Scholar
  24. 24.
    Mori Y, Murakawa Y, Okada K, Horikoshi H, Yokoyama J, Tajima N, Ikeda Y (1999) Effect of troglitazone on body fat distribution in type 2 diabetic patients. Diabetes Care 22:908–912PubMedCrossRefGoogle Scholar
  25. 25.
    Kudolo GB (2000) The effect of 3-month ingestion of Ginkgo biloba extract on pancreatic beta-cell function in response to glucose loading in normal glucose tolerant individuals. J Clin Pharmacol 40:647–654PubMedCrossRefGoogle Scholar
  26. 26.
    Taniguchi CM, Ueki K, Kahn R (2005) Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism. J Clin Invest 115:718–727PubMedGoogle Scholar
  27. 27.
    Kubota N, Tobe K, Terauchi Y, Eto K, Yamauchi T, Suzuki R, Tsubamoto Y, Komeda K, Nakano R, Miki H, Satoh S, Sekihara H, Sciacchitano S, Lesniak M, Aizawa S, Nagai R, Kimura S, Akanuma Y, Taylor SI, Kadowaki T (2000) Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory beta-cell hyperplasia. Diabetes 49:1880–1889PubMedCrossRefGoogle Scholar
  28. 28.
    Ide T, Shimano H, Yahagi N, Matsuzaka T, Nakakuki M, Yamamoto T, Nakagawa Y, Takahashi A, Suzuki H, Sone H, Toyoshima H, Fukamizu A, Yamada N (2004) SREBPs suppress IRS-2-mediated insulin signalling in the liver. Nat Cell Biol 6:351–357PubMedCrossRefGoogle Scholar
  29. 29.
    Lee YS, Cha BY, Saito K, Yamakawa H, Choi SS, Yamaguchi K, Yonezawa T, Teruya T, Nagai K, Woo JT (2010) Nobiletin improves hyperglycemia and insulin resistance in obese diabetic ob/ob mice. Biochem Pharmacol 79:1674–1683PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer 2010

Authors and Affiliations

  • Lei Zhou
    • 1
  • Qingjie Meng
    • 1
  • Tao Qian
    • 1
  • Zaiqing Yang
    • 1
  1. 1.Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of EducationCollege of Life Science and Technology, Huazhong Agricultural UniversityWuhanPeople’s Republic of China

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