title: Characterisation of the insulinotropic activity of an aqueous extract of Gymnema sylvestre in mouse beta-cells and human islets of Langerhans.
abstract: Leaves of the Gymnema sylvestre (GS) plant have been used to treat diabetes mellitus for millennia, but the previously documented insulin secretagogue effects of GS extracts in vitro may be non-physiological through damage to the beta-cells. We have now examined the effects of a novel GS extract (termed OSA) on insulin secretion from the MIN6 beta-cell line and isolated human islets of Langerhans. Insulin secretion from MIN6 cells was stimulated by OSA in a concentration-dependent manner, with low concentrations (0.06-0.25 mg/ml) having no deleterious effects on MIN6 cell viability, while higher concentrations (> or = 0.5 mg/ml) caused increased Trypan blue uptake. OSA increased beta-cell Ca2+ levels, an effect that was mediated by Ca2+ influx through voltage-operated calcium channels. OSA also reversibly stimulated insulin secretion from isolated human islets and its insulin secretagogue effects in MIN6 cells and human islets were partially dependent on the presence of extracellular Ca2+. These data indicate that low concentrations of the GS isolate OSA stimulate insulin secretion in vitro, at least in part as a consequence of Ca2+ influx, without compromising beta-cell viability. Identification of the component of the OSA extract that stimulates regulated insulin exocytosis, and further investigation of its mode(s) of action, may provide promising lead targets for Type 2 diabetes therapy.
authors.affiliation: Beta Cell Development & Function Group and Division of Gene & Cell Based Therapy, King's College London, UK.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Henry
authors.initials: H
authors.lastname: Asare-Anane
authors.forename: Altaf
authors.initials: A
authors.lastname: Al-Romaiyan
authors.forename: Guocai
authors.initials: G
authors.lastname: Huang
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Amiel
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jones
authors.forename: Shanta J
authors.initials: SJ
authors.lastname: Persaud
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D031104:Gymnema sylvestre / Q000737:chemistry*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008853:Microscopy; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D007328:Insulin; D010936:Plant Extracts; D014867:Water; D002118:Calcium