Comparative Effects of Stevia rebaudiana Leaves and Stevioside on Glycaemia and Hepatic Gluconeogenesis

Abstract

The purpose of the present study was to compare the effect of the oral treatment (gavage) with Stevia rebaudiana (Bert.) Bertoni (SRB) and stevioside (STV) on glycaemia and gluconeogenesis of 15-h fasted rats. For this purpose, the rats received SRB (20 mg/kg × day), STV (5.5 mg/kg × day) or an equal volume of water (controls) during 15 days. To measure hepatic gluconeogenesis, liver perfusion and isolated hepatocytes were used. Glycaemia and gluconeogenesis from L-alanine (5 mM), L-glutamine (5 mM) and L-lactate (2 mM) were decreased (P < 0.05) after pre-treatment with SRB. However, the treatment with STV did not influence glycaemia and gluconeogenesis. Moreover, to get further information about the mechanism by which SRB leaves inhibit gluconeogenesis their potential role as a PPARγ agonist was investigated. The data showed absence of activation of PPARγ receptors. In summary, our results showed that the reduction of glycaemia promoted by the treatment with SRB leaves was mediated, at least in part, by an inhibition of hepatic gluconeogenesis. However, this effect did not involve stevioside and the activation of PPARγ receptors.

Key words

Stevia rebaudiana (Bert) Bertoni - stevioside - gluconeogenesis - glycaemia - PPARγ agonist

References

• 1 Oviedo C A, Franciani G, Moreno R. Action hipoglucemiante de la Stevia rebaudiana Bertoni (Kaa-he-e). Seventh Congress of the International Diabetes Federation Buenos Aires, Argentina; 1970
• 2 Ueda M, Weffort R MM, Zubioli A, Bersani-Amado C A, Bazotte R B, Gaeti W P. et al . Efeito do extrato aquoso da Stevia rebaudiana (Bert) Bertoni sobre o teste de tolerância à glicose em ratos normais adultos.  Rev Unimar. 1983;  5 111-5
• 3 Curi R, Alvarez M, Bazotte R B. Effect of Stevia rebaudiana on glucose tolerance in normal adult humans.  Braz J Med Biol Res. 1986;  19 771-4
• 4 Jeppesen P B, Gregersen S, Poulsen C R, Hermansen K. Stevioside acts directly on pancreatic β cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K⁺ channel activity.  Metabolism. 2000;  49 208-14
• 5 Jeppesen P B, Gregersen S, Alstrup K K, Hermansen K. Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: studies in the diabetic Goto-Kakizaki (GK) rats.  Phytomedicine. 2002;  9 9-14
• 6 Jeppesen P B, Gregersen S, Rolfsen S E, Jepsen M, Colombo M, Agger A. et al . Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat.  . 2003;  52 372-8
• 7 Gregersen S, Jeppesen P B, Holst J J, Hermansen K. Antihyperglycemic effects of stevioside in type 2 diabetic subjects.  Metabolism. 2004;  53 73-6
• 8 Chang J C, Wu M C, Liu I M, Cheng J T. Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats.  . 2005;  37 610-6
• 9 Dyrskog S E, Jeppesen P B, Colombo M, Abudala R, Hermansen K. Preventive effects of a soy-based diet supplemented with stevioside on the development of the metabolic syndrome and type 2 diabetes in Zucker diabetic fatty rats.  Metabolism. 2005;  54 1181-8
• 10 Koyama E, Sakai N, Ohori Y, Kitazawa K, Izawa O, Kakegawa K. Absorption and metabolism of glycosidic sweeteners of stevia mixture and their aglycone, steviol, in rats and humans.  Food Chem Toxicol. 2003;  41 875-83
• 11 Geuns J MC, Augustijns P, Mols R, Buyse J G, Driessen B. Metabolism of stevioside in pigs and intestinal absorption characteristics of stevioside, rebaudioside A and steviol.  Food Chem Toxicol. 2003;  41 1599-607
• 12 Geuns J M. Stevioside.  Phytochemistry. 2003;  64 913-21
• 13 Murad G RB, Mario E G, Bassoli B K, Bazotte R B, Souza H M. Comparative acute effects of leptin and insulin on gluconeogenesis and ketogenesis in perfused rat liver.  Cell Biochem Funct. 2005;  23 405-13
• 14 Knouff C, Auwerx J. Peroxisome proliferator-activated receptor-gamma calls for activation in moderation: lessons from genetics and pharmacology.  Endocr Rev. 2004;  25 899-918
• 15 Evans R M, Barish G D, Wang Y X. PPARs and the complex journey to obesity.  Nat Med. 2004;  10 355-61
• 16 Togashi M, Ozawa S, Abe S, Nishimura T, Tsuruga M, Ando K. et al . Ascochlorin derivatives as ligands for nuclear hormone receptors.  J Med Chem. 2003;  46 4113-23
• 17 Alvarez M, Kusumoto I T. Análise quantitativa dos glicosídeos edulcorantes da Stevia rebaudiana e dos seus produtos de hidrolise através de cromatografia líquida de alta performance (HPLC).  Arq Biol Tecnol. 1987;  30 337-48
• 18 Bergmeyer H U, Bernt E. Determination of glucose with glucose oxidase and peroxidase. In: Bergmeyer HU, editor Methods of enzymatic analysis. Vol. 2 New York; Academic Press 1974: p 1205-15
• 19 Gutmann I, Wahlefeld W. L-(+)-Lactate. Determination with lactate dehydrogenase and NAD. In: Bermeyer HU, editor Methods of enzymatic analysis. Vol. 2 New York; Academic Press 1974: p 1464-72
• 20 Czok R, Lamprecht W. Pyruvate, phosphoenol pyruvate and D-glycerate 2-phosphate. In: Bermeyer HU, editor Methods of enzymatic analysis. Vol. 2 New York; Academic Press 1974: p 1446-8
• 21 Gutmann I, Bergmeyer H U. Determination of urea, indicator reaction with phenol and hypochlorite. In: Bermeyer HU, editor Methods of enzymatic analysis. Vol. 2 New York; Academic Press 1974: p 1790-8
• 22 Berry M N, Friend D S. High-yield preparation of isolated rat liver parenchymal cells. A biochemical and fine structural study.  J Cell Biol. 1969;  43 506-20
• 23 Bazotte R B. Obtenção de hepatócitos em perfusão de fígado de ratos in situ com colagenase. In: Peres CM, Curi R, editors Como Cultivar Células. Rio de Janeiro; Editora Guanabara Koogan 2005: p 75-7
• 24 Forman B M, Tontonoz P, Chen J, Brun R P, Spiegelman B M, Evans R. M15-deoxy-delta-12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma.  Cell. 1995;  83 803-12
• 25 Shapiro K, Gong W C. Natural products used for diabetes.  J Am Pharm Assoc. 2002;  42 217-26
• 26 Chen T H, Chen S C, Chan P, Chu Y L, Yang H Y, Cheng J T. Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana .  Planta Med. 2005;  71 08-13
• 27 Glorian M, Duplus E, Beale E G, Scott D K, Granner D K, Forest C. A single element in the phosphoenol pyruvate carboxykinase gene mediates thiazolidinedione action specifically in adipocytes.  Biochimie. 2001;  83 933-43
• 28 Mazzei-Planas G, Kuc J. Contraceptive properties of Stevia rebaudiana .  Science. 1968;  162 1007
• 29 Melis M S. Effects of chronic administration of Stevia rebaudiana on fertility in rats.  J Ethnopharmacol. 1999;  67 157-61
• 30 Oliveira-Filho R M, Uehara O A, Minetti C A, Valle L B. Chronic administration of aqueous extract of Stevia rebaudiana (Bert.) Bertoni in rats: endocrine effects.  Gen Pharmacol. 1989;  20 187-91
• 31 Shiotsu S. Fertility study of Stevia decoction in rats.  Tech J Food Chem Chemicals. 1996;  4 108-13
• 32 Darise M, Kohda H, Mizutam K, Kasai R, Tanaka O. Chemical constituents of flowers of Stevia rebaudiana Bertoni.  Agric Biol Chem. 1983;  47 133-5