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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.
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Article info
Publication history
Accepted:
July 21,
1999
Received:
March 25,
1999
Footnotes
Supported by the Danish Medical Research Council, Aarhus Amtssgehus Forskningsfond, and the Research Foundation of Aarhus University.
Identification
Copyright
© 2000 W.B. Saunders Company. Published by Elsevier Inc.
