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Planta Med 2023; 89(07): 735-745
DOI: 10.1055/a-2003-9463
Biological and Pharmacological Activity
Original Papers

Effects of Stevioside on the Expressions of GLUT 1, GLUT 3, and GLUT 4 Proteins in Diabetic Rat Placenta

Ertan Katirci 
Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
,
Remziye Kendirci-Katirci 
Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
,
Emin Turkay Korgun
Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
› InstitutsangabenThis study was supported by the Akdeniz University Scientific Research Projects Coordination Unit, project number TYL-2015 – 873.
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Abstract

The placenta provides maternal–fetal nutrient transport. The primary source of energy for fetus development is glucose and maternal–fetal glucose transport occurs through glucose transporters (GLUTs). Stevioside, a component of Stevia rebaudiana Bertoni, is used for medicinal and commercial purposes. We aim to determine the effects of stevioside on GLUT 1, GLUT 3, and GLUT 4 proteins expressions in diabetic rat placentas. The rats are divided into four groups. A single dose of streptozotocin (STZ) is administered to form the diabetic groups. Pregnant rats receive stevioside to form the stevioside and diabetic + stevioside groups. According to immunohistochemistry results, GLUT 1 protein is found in both the labyrinth and junctional zones. GLUT 3 protein is limited in the labyrinth zone. GLUT 4 protein is detected in trophoblast cells. According to Western blotting results, on the 15th and 20th days of pregnancy, there is no difference in the expression of GLUT 1 protein between groups. On the 20th day of pregnancy, the expression of GLUT 3 protein in the diabetic group is statistically higher compared to the control group. On the 15th day and 20th day of pregnancy, the expression of GLUT 4 protein in the diabetic group is statistically lower compared to the control group. Insulin levels in blood samples derived from rat abdominal aorta are determined by the ELISA method. According to the ELISA results, there is no difference in insulin protein concentration between groups. Stevioside treatment reduces GLUT 1 protein expression under diabetic conditions.

Key words

Stevia rebaudiana Bertoni - Asteraceae - stevioside - glucose transporter proteins - diabetic placenta - rat


Publikationsverlauf

Eingereicht: 06. September 2022

Angenommen nach Revision: 05. Dezember 2022

Artikel online veröffentlicht:
13. März 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Cross JC, Baczyk D, Dobric N, Hemberger M, Hughes M, Simmons DG, Yamamoto H, Kingdom JC. Genes, development and evolution of the placenta. Placenta 2003; 24: 123-130
    CrossrefPubMedSuche in Google Scholar
  • 2 Simmons DG, Fortier AL, Cross JC. Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta. Dev Biol 2007; 304: 567-578
    CrossrefPubMedSuche in Google Scholar
  • 3 Ain R, Canham LN, Soares MJ. Gestation stage-dependent intrauterine trophoblast cell invasion in the rat and mouse: novel endocrine phenotype and regulation. Dev Biol 2003; 260: 176-190
    CrossrefPubMedSuche in Google Scholar
  • 4 Soares MJ, Chapman BM, Rasmussen CA, Dai G, Kamei T, Orwig KE. Differentiation of trophoblast endocrine cells. Placenta 1996; 17: 277-289
    CrossrefPubMedSuche in Google Scholar
  • 5 Soares MJ, Konno T, Alam SM. The prolactin family: effectors of pregnancy-dependent adaptations. Trends Endocrinol Metab 2007; 18: 114-121
    CrossrefPubMedSuche in Google Scholar
  • 6 Köck K, Köck F, Klein K, Bancher-Todesca D, Helmer H. Diabetes mellitus and the risk of preterm birth with regard to the risk of spontaneous preterm birth. J Matern Fetal Neonatal Med 2010; 23: 1004-1008
    CrossrefPubMedSuche in Google Scholar
  • 7 Ruiz-Ruiz JC, Moguel-Ordoñez YB, Segura-Campos MR. Biological activity of Stevia rebaudiana Bertoni and their relationship to health. Crit Rev Food Sci Nutr 2017; 57: 2680-2690
    CrossrefPubMedSuche in Google Scholar
  • 8 Nathalie EL, Elena S, Mora-Escobedo R. A comprehensive review on the nutritional and therapeutical aspects of Stevia rebaudiana bertoni. JABB 2019; 6: 297-301
    CrossrefPubMedSuche in Google Scholar
  • 9 Akbarzadeh S, Eskandari F, Tangestani H, Bagherinejad ST, Bargahi A, Bazzi P, Daneshi A, Sahrapoor A, OʼConnor WJ, Rahbar AR. The effect of Stevia rebaudiana on serum omentin and visfatin level in STZ-induced diabetic rats. J Diet Suppl 2015; 12: 11-22
    CrossrefPubMedSuche in Google Scholar
  • 10 Assaei R, Mokarram P, Dastghaib S, Darbandi S, Darbandi M, Zal F, Akmali M, Ranjbar Omrani GH. Hypoglycemic effect of aquatic extract of stevia in pancreas of diabetic rats: PPARgamma-dependent regulation or antioxidant potential. Avicenna J Med Biotechnol 2016; 8: 65-74
    PubMedSuche in Google Scholar
  • 11 Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P, Williamson DA. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite 2010; 55: 37-43
    CrossrefPubMedSuche in Google Scholar
  • 12 Ferrando A, Vila L, Voces JA, Cabral AC, Alvarez AI, Prieto JG. Effects of a standardized Panax ginseng extract on the skeletal muscle of the rat: a comparative study in animals at rest and under exercise. Planta Med 1999; 65: 239-244
    Thieme ConnectPubMedSuche in Google Scholar
  • 13 Gawel-Beben K, Bujak T, Niziol-Lukaszewska Z, Antosiewicz B, Jakubczyk A, Karas M, Rybczynska K. Stevia rebaudiana Bert. leaf extracts as a multifunctional source of natural antioxidants. Molecules (Basel, Switzerland) 2015; 20: 5468-5486
    CrossrefPubMedSuche in Google Scholar
  • 14 Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K. Stevioside acts directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity. Metabolism 2000; 49: 208-214
    CrossrefPubMedSuche in Google Scholar
  • 15 Sukhmani G, Yogesh G, Shalini A, Vikas K, Anil P, Ashwani K. Natural sweeteners: Health benefits of stevia. FRM 2018; 6: 392-402
    CrossrefPubMedSuche in Google Scholar
  • 16 Gutiérrez DG, Muñoz-Schick M, Grossi MA, Rodríguez-Cravero JF, Morales V, Moreira-Muñoz A. The genus Stevia (Eupatorieae, Asteraceae) in Chile: a taxonomical and morphological analysis. Phytotaxa 2016; 282: 1-18
    CrossrefPubMedSuche in Google Scholar
  • 17 Chan P, Tomlinson B, Chen YJ, Liu JC, Hsieh MH, Cheng JT. A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension. Br J Clin Pharmacol 2000; 50: 215-220
    CrossrefPubMedSuche in Google Scholar
  • 18 Jeppesen PB, Gregersen S, Alstrup KK, Hermansen K. Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo: studies in the diabetic Goto-Kakizaki (GK) rats. Phytomedicine 2002; 9: 9-14
    CrossrefPubMedSuche in Google Scholar
  • 19 Lee KG, Shibamoto T. Inhibition of malonaldehyde formation from blood plasma oxidation by aroma extracts and aroma components isolated from clove and eucalyptus. Food Chem Toxicol 2001; 39: 1199-1204
    CrossrefPubMedSuche in Google Scholar
  • 20 Muanda FN, Soulimani R, Diop B, Dicko A. Study on chemical composition and biological activities of essential oil and extracts from Stevia rebaudiana Bertoni leaves. LWT 2011; 44: 1865-1872
    CrossrefPubMedSuche in Google Scholar
  • 21 Deenadayalan A, Subramanian V, Paramasivan V, Veeraraghavan VP, Rengasamy G, Coiambatore Sadagopan J, Rajagopal P, Jayaraman S. Stevioside attenuates insulin resistance in skeletal muscle by facilitating IR/IRS-1/Akt/GLUT 4 signaling pathways: An in vivo and in silico approach. Molecules 2021; 26: 7689
    CrossrefPubMedSuche in Google Scholar
  • 22 Rotimi SO, Rotimi OA, Adelani IB, Onuzulu C, Obi P, Okungbaye R. Stevioside modulates oxidative damage in the liver and kidney of high fat/low streptozocin diabetic rats. Heliyon 2018; 4: e00640
    CrossrefPubMedSuche in Google Scholar
  • 23 Jan SA, Habib N, Shinwari ZK, Ali M, Ali N. The anti-diabetic activities of natural sweetener plant stevia: An updated review. SN Applied Sciences 2021; 3: 517
    CrossrefPubMedSuche in Google Scholar
  • 24 Casas-Grajales S, Ramos-Tovar E, Chávez-Estrada E, Alvarez-Suarez D, Hernández-Aquino E, Reyes-Gordillo K, Cerda-García-Rojas CM, Camacho J, Tsutsumi V, Lakshman MR, Muriel P. Antioxidant and immunomodulatory activity induced by stevioside in liver damage: In vivo, in vitro and in silico assays. Life Sci 2019; 224: 187-196
    CrossrefPubMedSuche in Google Scholar
  • 25 Beneford DJ, Dinovi M, Schlatter J. Steviol glycosides. Safety evaluation of certain food additives. WHO Food Additive Series 2006; 54: 117-143
    PubMedSuche in Google Scholar
  • 26 Gutaj P, Wender-Ozegowska E. Diagnosis and management of IUGR in pregnancy complicated by type 1 diabetes mellitus. Curr Diab Rep 2016; 16: 39
    CrossrefPubMedSuche in Google Scholar
  • 27 Shafrir E, Barash V. Placental glycogen metabolism in diabetic pregnancy. Isr J Med Sci 1991; 27: 449-461
    PubMedSuche in Google Scholar
  • 28 Neʼeman Z, Barash V, Rosenmann E, Shafrir E. Localization of glycogen in the placenta of diabetic rats: A light and electron microscopic study. Placenta 1987; 8: 201-208
    CrossrefPubMedSuche in Google Scholar
  • 29 Tunster SJ, Watson ED, Fowden AL, Burton GJ. Placental glycogen stores and fetal growth: Insights from genetic mouse models. Reproduction 2020; 159: R213-R235
    CrossrefPubMedSuche in Google Scholar
  • 30 Akison LK, Nitert MD, Clifton VL, Moritz KM, Simmons DG. Review: Alterations in placental glycogen deposition in complicated pregnancies: Current preclinical and clinical evidence. Placenta 2017; 54: 52-58
    CrossrefPubMedSuche in Google Scholar
  • 31 Kalhan S, Parimi P. Gluconeogenesis in the fetus and neonate. Semin Perinatol 2000; 24: 94-106
    CrossrefPubMedSuche in Google Scholar
  • 32 Heazell AE, Lacey HA, Jones CJ, Huppertz B, Baker PN, Crocker IP. Effects of oxygen on cell turnover and expression of regulators of apoptosis in human placental trophoblast. Placenta 2008; 29: 175-186
    CrossrefPubMedSuche in Google Scholar
  • 33 Jansson T, Wennergren M, Powell TL. Placental glucose transport and GLUT 1 expression in insulin-dependent diabetes. Am J Obstet Gynecol 1999; 180: 163-168
    CrossrefPubMedSuche in Google Scholar
  • 34 Gutierrez-Torres DS, Gonzalez-Horta C, del Razo LM, Infante-Ramirez R, Ramos-Martinez E, Levario-Carrillo M, Sanchez-Ramirez B. Prenatal exposure to sodium arsenite alters placental glucose 1, 3, and 4 transporters in Balb/c mice. Biomed Res Int 2015; 2015: 175025
    CrossrefPubMedSuche in Google Scholar
  • 35 Ogura K, Sakata M, Yamaguchi M, Kurachi H, Murata Y. High concentration of glucose decreases glucose transporter-1 expression in mouse placenta in vitro and in vivo. J Endocrinol 1999; 160: 443-452
    CrossrefPubMedSuche in Google Scholar
  • 36 Korgun ET, Acar N, Sati L, Kipmen-Korgun D, Ozen A, Unek G, Ustunel I, Demir R. Expression of glucocorticoid receptor and glucose transporter-1 during placental development in the diabetic rat. Folia Histochem Cytobiol 2011; 49: 325-334
    CrossrefPubMedSuche in Google Scholar
  • 37 Boileau P, Mrejen C, Girard J, Hauguel-de Mouzon S. Overexpression of GLUT3 placental glucose transporter in diabetic rats. J Clin Invest 1995; 96: 309-317
    CrossrefPubMedSuche in Google Scholar
  • 38 Shin BC, Fujikura K, Suzuki T, Tanaka S, Takata K. Glucose transporter GLUT3 in the rat placental barrier: a possible machinery for the transplacental transfer of glucose. Endocrinology 1997; 138: 3997-4004
    CrossrefPubMedSuche in Google Scholar
  • 39 Brown K, Heller DS, Zamudio S, Illsley NP. Glucose transporter 3 (GLUT3) protein expression in human placenta across gestation. Placenta 2011; 32: 1041-1049
    CrossrefPubMedSuche in Google Scholar
  • 40 Lesage J, Hahn D, Léonhardt M, Blondeau B, Bréant B, Dupouy JP. Maternal undernutrition during late gestation-induced intrauterine growth restriction in the rat is associated with impaired placental GLUT3 expression, but does not correlate with endogenous corticosterone levels. J Endocrinol 2002; 174: 37-43
    CrossrefPubMedSuche in Google Scholar
  • 41 Jansson T, Wennergren M, Illsley NP. Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation. J Clin Endocrinol Metab 1993; 77: 1554-1562
    CrossrefPubMedSuche in Google Scholar
  • 42 Illsley NP. Glucose transporters in the human placenta. Placenta 2000; 21: 14-22
    CrossrefPubMedSuche in Google Scholar
  • 43 Ganguly A, Collis L, Devaskar SU. Placental glucose and amino acid transport in calorie-restricted wild-type and Glut3 null heterozygous mice. Endocrinology 2012; 153: 3995-4007
    CrossrefPubMedSuche in Google Scholar
  • 44 Prata C, Zambonin L, Rizzo B, Maraldi T, Angeloni C, Vieceli Dalla Sega F, Fiorentini D, Hrelia S. Glycosides from stevia rebaudiana bertoni possess insulin-mimetic and antioxidant activities in rat cardiac fibroblasts. Oxid Med Cell Longev 2017; 2017: 3724545
    CrossrefPubMedSuche in Google Scholar
  • 45 Rizzo B, Zambonin L, Angeloni C, Leoncini E, Dalla Sega FV, Prata C, Fiorentini D, Hrelia S. Steviol glycosides modulate glucose transport in different cell types. Oxid Med Cell Longev 2013; 2013: 348169
    CrossrefPubMedSuche in Google Scholar
  • 46 Catalano PM. Trying to understand gestational diabetes. Diabet Med 2014; 31: 273-281
    CrossrefPubMedSuche in Google Scholar
  • 47 Chang YL, Chao AS, Chang SD, Cheng PJ. Placental glucose transporter 1 and 3 gene expression in Monochorionic twin pregnancies with selective fetal growth restriction. BMC Pregnancy Childbirth 2021; 21: 260
    CrossrefPubMedSuche in Google Scholar
  • 48 Perumal V, Manickam T, Bang KS, Velmurugan P, Oh BT. Antidiabetic potential of bioactive molecules coated chitosan nanoparticles in experimental rats. Int J Biol Macromol 2016; 92: 63-69
    CrossrefPubMedSuche in Google Scholar
  • 49 Jeppesen PB, Gregersen S, Rolfsen SE, Jepsen M, Colombo M, Agger A, Xiao J, Kruhøffer M, Orntoft T, Hermansen K. Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat. Metabolism 2003; 52: 372-378
    CrossrefPubMedSuche in Google Scholar
  • 50 Jeppesen PB, Dyrskog SE, Agger A, Gregersen S, Colombo M, Xiao J, Hermansen K. Can stevioside in combination with a soy-based dietary supplement be a new useful treatment of type 2 diabetes? An in vivo study in the diabetic goto-kakizaki rat. Rev Diabet Stud 2006; 3: 189-199
    CrossrefPubMedSuche in Google Scholar
  • 51 Suanarunsawat T, Klongpanichapak S, Rungseesantivanon S, Chaiyabutr N. Glycemic effect of stevioside and Stevia rebaudiana in streptozotocin-induced diabetic rats. East J Med 2004; 9: 51-56
    PubMedSuche in Google Scholar
  • 52 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275
    CrossrefPubMedSuche in Google Scholar
  • 53 Zou X, Tan Q, Goh BH, Lee LH, Tan KL, Ser HL. ‘Sweeter’ than its name: anti-inflammatory activities of Stevia rebaudiana. All Life 2020; 13: 286-309
    CrossrefPubMedSuche in Google Scholar