Skip to main content
SpringerLink
Log in

Effect of stevioside and sodium salt of monoketocholic acid on glycemia in normoglycemic and diabetic rats

  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Summary

This study investigated the effect of a commercial preparation of stevioside and a synthetic compound, sodium salt of monketocholic acid (MKC), administered per os (p.o.) and also adminstered via an osmotic pump, on glycemia in normoglycemic and diabetic Wistar rats. Diabetes was induced with alloxan, 100 mg/kg, i.p. Normoglycemic and diabetic rats were treated p.o. for five days either with physiological solution (1 ml/kg, controls), stevioside (20 mg/kg), MKC (4 mg/kg) and a combination of stevioside (20 mg/kg) and MKC (4 mg/kg). Apart from p.o. adminstration, stevioside and MKC were also administered via a subcutaneously (s.c.) implanted osmotic pump. During treatment and upon termination of the latter, glycemia was measured and the rats that were treated p.o. were subjected to the oral glucose tolerance test (OGTT) at a dose of 1 g/kg. Following this animals were anesthetized with urethane (0.75 g/kg, i.p.) and killed by cardiopunction to determine C-peptide levels in the serum. In all three groups of normoglycemic rats highest decrease in glucose levels was observed on the fourth day of the experiment. The stevioside + MKC combination showed a stronger hypoglycemic effect compared to individual treatments with stevioside and MKC (3.73:4.80:4.73 mmol/L). In the group of diabetic rats that received both substances via the osmotic pump, the hypoglycemic action was also stronger compared to the individual treatments with stevioside and MKC (16.15:18.89:18.75 mmol/L). The treatment of healthy rats with both substances p.o. caused no statistically significant difference in glycemia, whereas in diabetic rats the combination of stevioside + MKC showed a statistically significant decrease in glycemia compared to control values. In both groups of rats, treatment with stevioside and MKC and their combination prevented an increase in glucose concentrations in the OGTT. Only the administration of stevioside by osmotic pump yielded a statistically significant increase in the concentrations of C-peptide in the serum of healthy rats. Compared to controls, the concentrations of C-peptide in diabetic rats were significantly higher after treatment with either stevioside or its combination with MKC, irrespective of the mode of administration.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lappesen P.B., Gregersen S., Alstrup K.K., Hermansen K. (2002): Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: studies in the diabetic Goto-Kakazaki rats. Phytomedicine, 9:9–14.

    Article  Google Scholar 

  2. Gregersen S., Jappesen P.B., Holst J.J., Hermansen K. (2004): Antihyperglycemic effect of stevioside in type 2 diabetic subjects. Metabolism, 53:73–76.

    Article  CAS  PubMed  Google Scholar 

  3. Lailerd N., Saengsirisuwan V., Sloniger J.A. (2004). Effect of stevioside on glucose transport activity in insulin-sensitive and insulin-resistant rat skeletal muscle. Metabolism, 53:101–107.

    Article  CAS  PubMed  Google Scholar 

  4. Abudula R., Jeppesen P.B., Rolfsen S.E., Xiao J., Hermansen K. (2004): Rebaudioside A potently stimulates insulin secretion from isolated mouse islets: studies on the dose-, glucose-, and calcium-dependency. Metabolism, 53:137–181.

    Article  Google Scholar 

  5. Fabiani E., Mitro N., Godio C. (2004): Bile acid signaling to the nucleus: finding new connections in the transcriptional regulation of metabolic pathways. Biochimie, 86:771–778.

    Article  PubMed  Google Scholar 

  6. Raskovic A., Gavrilovic M., Jakovljevic V., Sabo J. (2004): Glucose Concentration in the blood of intact and alloxan-treated mice after pretreatment with commercial preparations ofStevia rebaudiana (Bertoni). Eur. J. Drug Metab. Pharmacokinet., 29:87–90.

    Article  CAS  PubMed  Google Scholar 

  7. Fabiani E., Mitro N., Gilardo F. (2003): Coordinated control of cholesterol catabolism to bile acids and of gluconeogenesis via a novel mechanism of transcription regulation linked to the fasted-to fed cycle. J. Biol. Chem., 278:39124–39132.

    Article  PubMed  Google Scholar 

  8. Fabiani E., Mitro N., Godio C. (2004): Bile acid signaling to the nucleus: finding new connections in the transcriptional regulation of metabolic pathways. Biochimie, 86:771–778.

    Article  PubMed  Google Scholar 

  9. Kuhajda K., Kevresan S., Mikov M. (1997): 3α,7α-dihydroxy-12-keto-5β-cholanate as an enhancer of insulin nasal absorption in rats. Arch. Toxicol. Kinet. Xenobiotic Metab., 5:359–361.

    Google Scholar 

  10. Mikov M., Fawcett J.P. (editors) (2007): Bile acids: chemistry, biosynthesis, analysis, chemical and metabolic transformations. Mediset Publisher, Geneva.

    Google Scholar 

  11. Mikov M., Boni N.S., Al-Salami H., Kuhajda K., Kevresan S., Golocorbin-Kon S., Fawcett J.P. (2007): Bio-availability and hypoglycaemic activity of the semisynthetic bile acid 3-alfa, 7-alfa-dihydroxy-12-oxo-5-beta-cholanate, in healthy and diabetic rats. Eur. J. Drug Metab. Pharmacokinet., 32:7–12.

    CAS  PubMed  Google Scholar 

  12. Mikov M., Fawcett J.P., Kuhajda K., Kevresan S. (2006): Pharmacology of bile acids and their derivatives: absorption promoters and therapeutic agents. Eur. J. Drug Metab. Pharmacokinet., 31:237–251.

    Article  CAS  PubMed  Google Scholar 

  13. Mikov M., Fawcett J.P., Kuhajda K., Kevresan S. (2006): Pharmacology of bile acids and their derivatives: absorption promoters and therapeutic agents. Eur. J. Drug Metab. Pharmacokinet., 31:237–251.

    Article  CAS  PubMed  Google Scholar 

  14. Mikov M., Kuhajda K., Kandrac J. (2003): New trends in therapeutic application of bile acids. Med. Pregled, 56:237–242.

    Article  Google Scholar 

  15. Kuhajda K., Kevresan S., Mikov M., Miljkovic D. (2000): Influence of 3-alfa, 7-alfa dihydroxy -12-oxo- 5-beta cholanate on blood glucose levels in rats. Arch. Toxicol. Kinet. Xenobiot. Metab. 8:304–308.

    Google Scholar 

  16. Raskovic A., Jakovljevic V., Mikov M., Gavrilovic M. (2004): Joint effect of commercial preparations ofStevia rebaundiana Bertoni and sodium monoketocholate on glycaemia in mice. Eur. J. Drug. Metab. Pharmacokinet., 29: 83–86.

    Article  CAS  PubMed  Google Scholar 

  17. Jappesen P.B., Gregersen S., Alstrup K.K., Hermansen K. (2002): Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: studies in the diabetic Goto-Kakizaki rats. Phytomedicine, 9:73–76.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept of Pharmacology, Toxicology and Clinical Pharmacology, School of Medicine, University of Novi Sad, 21 000, Hajduk Veljkova 3, Novi Sad

    Aleksandar Rašković, Vida Jakovljević, Velibor Vasović, Mihalj Posa & Zdenko Tomic

  2. School of Pharmacy, University of Otago, New Zealand

    Momir Mikov

  3. Department of Phrmacology, School of Medicine, University of Banja Luka, Republic of Bosnia and Hercegovina

    Ranko Škrbić

  4. Pharmacy of Scienties, University of Novi Sad, Republic of Serbia

    Ksenlia Kuhajda

  5. Faculty of Agriculture, Clinical Center, Novi Sad, Republic of Serbia

    Slavko Kevrešan

  6. Clinic for Psychiatry, Clinical Center, Novi Sad, Republic of Serbia

    Djendji Siladji

Authors
  1. Aleksandar Rašković
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Momir Mikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ranko Škrbić
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vida Jakovljević
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Velibor Vasović
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mihalj Posa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ksenlia Kuhajda
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Slavko Kevrešan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zdenko Tomic
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Djendji Siladji
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rašković, A., Mikov, M., Škrbić, R. et al. Effect of stevioside and sodium salt of monoketocholic acid on glycemia in normoglycemic and diabetic rats. Eur. J. Drug Metabol. Pharmacokinet. 33, 17–22 (2008). https://doi.org/10.1007/BF03191014

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03191014

Key words

Search

Navigation