Probiotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats

Summary

The action of gliclazide, a sulphonylurea with beneficial extrapancreatic effects in diabetes, may be enhanced by administering probiotics. The aim of this study was to investigate the influence of probiotics on gliclazide pharmacokinetics and the effect of both probiotics and gliclazide on blood glucose levels in healthy and diabetic rats. Male Wistar rats (2 to 3 months, weight 350 ± 50 g) were randomly allocated to 4 groups (n =10), two of which were treated with alloxan i.v. 30 mg/kg to induce diabetes. One group of healthy and one group of diabetic rats were then gavaged with probiotics (75 mg/kg) for three days after which a gliclazide suspension (20 mg/kg) was administered by gavage to all groups. Blood samples were collected from the tail vein at various time points for 10 hours post-administration for the determination of blood glucose and gliclazide serum concentrations. It was found that probiotic treatment had no effect on blood glucose levels in healthy rats, but it reduced them (up to 2-fold;p < 0.01) in diabetic rats. Probiotic treatment reduced gliclazide bioavailability in healthy rats (3-fold) whereas it increased gliclazide bioavailability in diabetic rats (2-fold;p < 0.01). Gliclazide had no effect on blood glucose levels in either healthy or diabetic rats despite the changes in its bioavailability. In conclusion, the probiotic treatment of diabetic rats increases gliclazide bioavailability and lowers blood glucose levels by insulin-independent mechanisms, suggesting that the administration of probiotics may be beneficial as adjunct therapy in the treatment of diabetes.

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References

  1. 1.

    FAOA/WHO. (2002): Guidelines for the Evaluation of Probiotics in Food. Report on drafting guidelines for the evaluation of probiotics in food. Ontario, Canada.

  2. 2.

    Bezkorovainy A. (2001): Probiotics: determinants of survival and growth in the gut. Am. J. Clin. Nutr., Suppl (2), 399–405.

    Google Scholar 

  3. 3.

    Karimi O., Pena A. (2003): Probiotics: Isolated bacteria strain or mixtures of different strains? Two different approaches in the use of probiotics as therapeutics. Drugs Today, 39, 565–597.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Billoo A., Memon M., Khaskheli S.A., Murtaza G., Iqbal K., Saeed Shekhani M., et al (2003): Role of a probiotic (Saccharomyces boulardii) in management and prevention of diarrhoea. World. J. Gastroenterol., 6, 4557–4560.

    Google Scholar 

  5. 5.

    Mikov M. (1994): The metabolism of drugs by the gut flora. Eur. J. Drug. Metab. Pharmacokinet., 19, 201–207.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Ghosh S., van Heel D., Playford R.J. (2004): Probiotics in inflammatory bowel disease: is it all gut flora modulation? Gut, 53, 620–622.

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Schultz M., Linde H.J., Lehn N., Zimmermann K., Grossmann J., Falk W., et al. (2003): Immunomodulatory consequences of oral administration ofLactobacillus rhamnosus strain GG in healthy volunteers. J. Dairy. Res., 70, 165–173.

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Gill H.S., Rutherfurd K.J., Prasad J., Gopal P.K. (2000): Enhancement of natural and acquired immunity byLactobacillus rhamnosus (HN001),Lactobacillus acidophilus (HN017) andBifidobacterium lactis (HN019). Br. J. Nutr., 83, 167–176.

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Onkamo P., Vaananen S., Karvonen M., Tuomilehto J. (1999): Worldwide increase in incidence of type I diabetes— the analysis of the data on published incidence trends. Diabetologia, 42, 1395–1403.

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Pundziute-Lycka A., Dahlquist G., Nystrom L, Arnqvist H., Bjork E., Blohme G., et al. (2002): The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0–34 years group in Sweden 1983–1998. Diabetologia, 45, 783–791.

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Libman I., Songer T., LaPorte R. (1993): How many people in the U.S. have IDDM?. Diabetes Care, 16, 841–852.

    CAS  PubMed  Google Scholar 

  12. 12.

    Bourlioux P., Koletzko B., Guarner F., Braesco V. (2003): The intestine and its microflora are partners for the protection of the host. Am. J. Clin. Nutr., 78, 675–683.

    CAS  PubMed  Google Scholar 

  13. 13.

    Calcinaro F., Dionisi S., Marinaro M., Candeloro P., Bonato V., Marzotti S., et al. (2005): Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse. Diabetologia, 48, 1565–1575.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Rendali M. (2004): The role of sulphonylureas in the management of type 2 Diabetes Mellitus. Drugs, 64, 1349–1358.

    Google Scholar 

  15. 15.

    Yaris F., Yaris E., Kadioglu M., Ulku C, Kesim M., Kalyoncu N.I. (2004): Normal pregnancy outcome following inadvertent exposure to rosiglitazone, gliclazide, and atorvastatin in a diabetic and hypertensive woman. Reprod. Toxicol., 18, 619–621.

    CAS  PubMed  Google Scholar 

  16. 16.

    Campbell D.B., Lavielle R., Nathan C. (1991): The mode of action and clinical pharmacology of gliclazide: a review. Diabetes. Res. Clin. Pract., 14, Suppl 2, 21–36.

    Article  Google Scholar 

  17. 17.

    Smith R.J. (1990): Effects of the sulfonylureas on muscle glucose homeostasis. Am. J. Med., 89, 38S-43S.

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Renier G., Desfaits A.C., Serri O. (2000): Effect of gliclazide on monocyte-endothelium interactions in diabetes. J. Diabetes Complications, 14, 215–223.

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Palmer K.J., Brogden R.N. (1993): Gliclazide. An update of its pharmacological properties and therapeutic efficacy in non-insulin-dependent diabetes mellitus. Drugs, 46, 92–125.

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Al-Salami H., Butt G., Tucker I., Mikov M. (2008): Influence of the semisynthetic bile acid MKC on the ileal permeation of gliclazidein vitro in healthy and diabetic rats treated with probiotics. Methods. Find. Exp. Clin. Pharmacol., 30, 1–7.

    Article  Google Scholar 

  21. 21.

    Carvalhol E., Carvalhol S., Ferreira. L.M. (2003): Experimental model of induction of diabetes mellitus in rats. Acta Cirurg. Bras., 18, 120–167.

    Google Scholar 

  22. 22.

    Korec R. (1980): Treatment of alloxan and streptozotocin diabetes in rats by intrafamiliar homo (allo) transplantation of neonatal pancreases. Endocrinol. Exp., 14, 191–198.

    CAS  PubMed  Google Scholar 

  23. 23.

    Stetinova V., Kvetina J., Pastera J., Polaskova A., Prazakova M. (2007): Gliclazide: pharmacokinetic-pharmacodynamic relationships in rats. Biopharm. Drug Dispos., 28, 241–248.

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Bachmann K., Pardoe D., White D. (1996): Scaling basic toxicokinetic parameters from rat to man. Environ. Health. Perspect., 104, 400–407.

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Alam M.J., Rahman M.A. (1971): Changes in the saccharoid fraction in rats with alloxan-induced diabetes or injected with epinephrine. Clin. Chem., 17, 915–920.

    CAS  PubMed  Google Scholar 

  26. 26.

    Khavinson V.K. (2005): Effect of tetrapeptide on insulin biosynthesis in rats with alloxan-induced diabetes. Bull. Exp. Biol. Med., 140, 452–454.

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Park J.Y., Kim K.A., Park P.W., Park C.W., Shin J.G. (2003): Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide. Clin. Pharmacol. Ther., 74, 334–340.

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Rouini M.R., Mohajer A., Tahami M.H. (2003): A simple and sensitive HPLC method for determination of gliclazide in human serum. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sei., 785, 383–386.

    Article  CAS  Google Scholar 

  29. 29.

    Drucker D.J. (2001): Minireview: the glucagon-like peptides. Endocrinology, 142, 521–527.

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    Drucker D.J. (2007): The role of gut hormones in glucose homeostasis. J. Clin. Invest., 117, 24–32.

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Bansil R., Stanley E., LaMont J.T. (1995): Mucin biophysics. Annu. Rev. Physiol. 57, 635–657.

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Ceriello A. (2006): Effects of gliclazide beyond metabolic control. Metabolism 55, Suppl 1, S5–10.

    Google Scholar 

  33. 33.

    Da Tos V., Maran A., Vigili De Kreutzenberg. Marchetto S., Tadiotto F., Bettio M. (2000): Mechanisms of acute and chronic hypoglycemic action of gliclazide. Acta. Diabetol. 37, 201–206.

    Article  PubMed  Google Scholar 

  34. 34.

    Delrat P., Paraire M., Jochemsen R. (2002): Complete bioavailability and lack of food-effect on pharmacokinetics of gliclazide 30 mg modified release in healthy volunteers. Biopharm. Drug. Dispos., 23, 151–157.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Momir Mikov.

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Al-Salami, H., Butt, G., Fawcett, J.P. et al. Probiotic treatment reduces blood glucose levels and increases systemic absorption of gliclazide in diabetic rats. Eur. J. Drug Metabol. Pharmacokinet. 33, 101–106 (2008). https://doi.org/10.1007/BF03191026

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Key words

  • Diabetes
  • probiotics
  • gliclazide
  • pharmacokinetics
  • blood glucose