Advertisement

Stevioside acts directly on pancreatic β cells to secrete insulin: Actions independent of cyclic adenosine monophosphate and adenosine triphosphate—sensitivie K+-channel activity

  • P.B. Jeppesen
    Correspondence
    Address reprint requests to P.B. Jeppesen, MSci, Department of Endocrinology and Metabolism, Aarhus University Hospital, Tage-Hansens gade 2, DK-8000 Aarhus C, Denmark.
    Affiliations
    Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark

    Islet Cell Physiology, Novo Nordisk, Copenhangen, Denmark
    Search for articles by this author
  • S. Gregersen
    Affiliations
    Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark

    Islet Cell Physiology, Novo Nordisk, Copenhangen, Denmark
    Search for articles by this author
  • C.R. Poulsen
    Affiliations
    Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark

    Islet Cell Physiology, Novo Nordisk, Copenhangen, Denmark
    Search for articles by this author
  • K. Hermansen
    Affiliations
    Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark

    Islet Cell Physiology, Novo Nordisk, Copenhangen, Denmark
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      The natural sweetener stevioside, which is found in the plant Stevia rebaudiana Bertoni, has been used for many years in the treatment of diabetes among Indians in Paraguay and Brazil. However, the mechanism for the blood glucose—lowering effect remains unknown . To elucidate the impact of stevioside and its aglucon steviol on insulin release from normal mouse islets and the β-cell line INS-1 were used. Both stevioside and steviol (1 nmol/L to 1 mmol/L) dose-dependently enhanced insulin secretion from incubated mouse islets in the presence of 16.7 mmol/L glucose (P < .05). The insulinotropic effects of stevioside and steviol were critically dependent on the prevailing glucose concentration, ie, stevioside (1 mmol/L) and steviol (1 μmol/L) only potentiated insulin secretion at or above 8.3 mmol/L glucose (P < .05). Interestingly, the insulinotropic effects of both stevioside and steviol were preserved in the absence of extracellular Ca2+. During perifusion of islets, stevioside (1 mmol/L) and steviol (1 μmol/L) had a long-lasting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). To determine if stevioside and steviol act directly on β cells, the effects on INS-1 cells were also investigated. Stevioside and steviol both potentiated insulin secretion from INS-1 cells (P < .05). Neither stevioside (1 to 100 μmol/L) nor steviol (10 nmol/L to 10 μmol/L) influenced the plasma membrane K+ adenosine triphosphate (KATP+)-sensitive channel activitiy, nor did they alter cyclic adenosine monophosphate (cAMP) levels in islets. In conclusion, stevioside and steviol stimulate insulin secretion via a direct action on β cells. The results indicate that the compounds may have a potential role as antihyperglycemic agents in the treatment of type 2 diabetes mellitus.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Metabolism - Clinical and Experimental
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bridel M
        • Lavielle R
        Physiologie Vegetale.
        in: Sur le principe sucre'du Kaa'-he'-e' (Stevia rebaudiana Bertoni): Il Les produits d'hydrolyse diastasique du stevioside, glucose et steviol. Acad Sci Paris. 192. 1931: 1123-1125
        • Soejarto DD
        • Kinghorn AD
        • Farnsworth NR
        Potential sweetening agents of plant origin. III. Organo leptic evaluation of Stevia leaf herbarium samples for sweetness.
        J Nat Prod. 1983; 45: 590-598
        • Mosettig E
        • Nes WR
        Stevioside. II. The structure of the aglucone.
        J Org Chem. 1955; 20: 884-899
        • Kohda H
        • Hasai R
        • Yamasaki K
        • et al.
        New sweet diterpene glucosides from Stevia rebaudiana.
        Phytochemistry. 1976; 15: 981-983
        • Sakaguschi M
        • Kan P
        Aspesquisas japonesas com Stevia reboudiana (Bert) Bertoni e o estevioside.
        Cienc Cultur. 1982; 34: 235-248
      1. (abstr 208)
        • Oviedo CA
        • Franciani G
        • Moreno R
        • et al.
        Action hipoglucemiante de la Stevia rebaudiana Bertoni (Kaa-he-e).
        in: Seventh Congress of the International Diabetes Federation, Buenos Aires, Argentina1970
        • Curi R
        • Alvarez M
        • Bazotte RB
        • et al.
        Effect of Stevia rebaudiana on glucose tolerance in normal adult humans.
        Braz J Med Biol Res. 1986; 19: 771-774
        • Hanson JR
        • Oliveira BH
        Stevioside and related sweet diterpenoid glycosides.
        Nat Prod Rep. 1993; 21: 301-309
        • Lacy PE
        • Kostianovsky M
        Methods for the isolation of intact islets of Langerhans from the rat pancreas.
        Diabetes. 1967; 16: 35-39
        • Gregersen S
        • Thomsen JL
        • Brock B
        • et al.
        Endothelin-1 stimulates insulin secretion by direct action on the islets of Langerhans in mice.
        Diabetologia. 1996; 39: 1030-1035
        • Asfari M
        • Janjic D
        • Meda P
        • et al.
        Establishment of 2-mercaptoethanol—dependent differentiated insulin-secreting cell lines.
        Endocrinology. 1992; 130: 167-177
        • Rorsman P
        • Trube G
        Calcium and delayed potassium currents in mouse pancreatic beta-cells under voltage-clamp conditions.
        J Physiol (Lond). 1986; 374: 531-550
        • Hamill OP
        • Marty A
        • Neher E
        • et al.
        Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
        Pflugers Arch. 1981; 391: 85-100
        • Gilon P
        • Henquin JC
        Influence of membrane potential changes on cytoplasmic Ca2+ concentration in an electrically excitable cells, the insulin-secreting pancreatic B-cell.
        J Biol Chem. 1992; 267: 20713-20720
        • Bailey CJ
        • Day C
        Traditional medicines in the treatment of diabetes.
        Diabetes Care. 1989; 12: 553-564
        • Oubre AY
        • Carlson TJ
        • King SR
        • et al.
        From plant to patient: An ethnobotanical approach to the identification of new drugs for the treatment of NIDDM.
        Diabetologia. 1997; 40: 614-617
        • Usami M
        • Seino Y
        • Takai J
        • et al.
        Effect of cyclamate sodium, saccharin sodium and stevioside on arginine-induced insulin and glucagon secretion in the isolated perfused rat pancreas.
        Horm Metab Res. 1980; 12: 705-706
        • Meinert L
        • Knatterud GL
        • Proute TE
        • University Group Diabetés Program
        A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results.
        Diabetes. 1970; 19: 789-830
        • Geisen K
        • Vegh A
        • Krause E
        Cardiovascular effects of conventional sulfonylureas and glimepiride.
        Horm Metab Res. 1996; 28: 496-507
        • Gromada J
        • Holst JJ
        • Rorsman P
        • et al.
        Cellular regulaton of hormone secretion by the incretin hormone glucagon-like peptide 1.
        Pflugers Arch. 1998; 435: 583-594
        • Suanarunsawat H
        • Chaiyabutr TN
        The effect of stevioside on glucose metabolism in rat.
        Can J Physiol Pharmacol. 1997; 75: 976-982
        • Vignais PV
        • Duee EDE
        • Vignais PM
        • et al.
        Effect of atractyligenin and its structural analogues on oxidative phosphorylation and on the translocation of adenine nucleotides in mitochondria.
        Biochim Biophys Acta. 1966; 118: 465-483
        • Bracht AK
        • Alvarez M
        • Bracht A
        Effect of Stevia rebaudiana natural products on rat liver mitochondria.
        Biochem Pharmacol. 1985; 34: 873-882
        • Yamamoto NS
        • Bracht AMK
        • Ishii EL
        • et al.
        Effect of steviol and its structural analogues on glucose production and oxygen uptake in rat renal tubules.
        Experientia. 1985; 41: 55-57