title: Stevioside does not cause increased basal insulin secretion or beta-cell desensitization as does the sulphonylurea, glibenclamide: studies in vitro.
abstract: We have shown that stevioside (SVS) enhances insulin secretion and thus may have a potential role as antihyperglycemic agent in the treatment of type 2 diabetes mellitus. However, whether SVS stimulates basal insulin secretion (BIS) and/or cause desensitization of beta cells like sulphonylureas (SU), e.g. glibenclamide (GB), is not known. To explore and compare the effects of SVS pretreatment with those of GB and glucagon-like peptide-1 (GLP-1), we exposed isolated mouse islets to low or high glucose for 1 h after short-term (2 h) or long-term (24 h) pretreatment with SVS, GB or GLP-1, respectively. BIS at 3.3 or 5.5 mM glucose were not changed after short-term pretreatment with SVS (10(-7) M), while it increased about three folds after pretreatment with GB (10(-7) M). Glucose stimulated insulin secretion (GSIS) (16.7 mM) increased dose-dependently after long-term pretreatment with SVS at concentrations from 10(-7) to 10(-5) M. Pretreatment for 24 h with GB (10(-7) M) increased the subsequent BIS (3.3 mM glucose) (p < 0.001), but decreased GSIS (16.7 mM glucose) (p < 0.001). In contrast SVS (10(-7) M) and GLP-1 (10(-7) M) did not stimulate BIS but both enhanced the subsequent GSIS (16.7 mM glucose) (p < 0.05 and p < 0.05, respectively). While SVS pretreatment increased the intracellular insulin content, GB pretreatment decreased the insulin content. Our study suggests that SVS pretreatment does not cause a stimulation of BIS and does not desensitize beta-cells, i.e. SVS seems to have advantageous characteristics to GB as a potential treatment of type 2 diabetes.
authors.affiliation: Department of Endocrinology and Metabolism, Aarhus Sygehus THG, Aarhus University Hospital, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark. jianguo.chen@ki.au.dk
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.forename: Per Bendix
authors.initials: PB
authors.lastname: Jeppesen
authors.forename: Reziwanggu
authors.initials: R
authors.lastname: Abudula
authors.forename: Stig E U
authors.initials: SE
authors.lastname: Dyrskog
authors.forename: Michele
authors.initials: M
authors.lastname: Colombo
authors.forename: Kjeld
authors.initials: K
authors.lastname: Hermansen
mesh_terms: D000818:Animals; D045786:Diterpenes, Kaurane / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005960:Glucosides / Q000009:adverse effects / Q000494:pharmacology*; D005905:Glyburide / Q000009:adverse effects / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D045786:Diterpenes, Kaurane; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; C012043:stevioside; D005947:Glucose; D005905:Glyburide