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Investigation of intracellular signalling cascades mediating stimulatory effect of a Gymnema sylvestre extract on insulin secretion from isolated mouse and human islets of Langerhans

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)1104-1113
Issue number12
Early online date1 Aug 2012
E-pub ahead of print1 Aug 2012
PublishedDec 2012

King's Authors


AIM: Traditional plant-based remedies such as Gymnema sylvestre (GS) extracts have been used to treat diabetes mellitus for many centuries. We have shown previously that a novel GS extract, OSA®, has a direct effect on insulin secretion but its mode of action has not been studied in detail Thus this study investigated the possible underlying mechanism(s) by which OSA® exerts its action.

METHODS: The effects of OSA® on [Ca(2+) ](i) and K(+) conductances were assessed by Ca(2+) microfluorimetry and electrophysiology in dispersed mouse islets and MIN6 β-cells, respectively. Isolated mouse (from 20 to 25 mice) and human (from 3 donors) islets, and MIN6 β-cells, were used to investigate whether the stimulatory effect of OSA® on insulin secretion was dependent on the presence of extracellular calcium and protein kinase activation.

RESULTS: OSA ®-induced insulin secretion from mouse islets and MIN6 β-cells was inhibited by nifedipine, a voltage-gated Ca(2+) channel blocker, and by the removal of extracellular Ca(2+) , respectively. OSA® did not affect the activities of K(ATP) channels or voltage-dependent K(+) channels in MIN6 β-cells but it caused an increase in intracellular Ca(2+) ([Ca(2+) ](i) ) concentrations in Fura-2-loaded mouse islet cells. The insulin secretagogue effect of OSA® was dependent, in part, on protein kinase activation since incubating mouse or human islets with staurosporine, a general protein kinase inhibitor, resulted in partial inhibition of OSA®-induced insulin secretion. Experiments using permeabilized, Ca(2+) -clamped MIN6 β-cells revealed a Ca(2+) -independent component action of OSA® at a late stage in the stimulus-response coupling pathway. OSA®-induced insulin secretion was unexpectedly associated with a decrease in intracellular cAMP levels.

CONCLUSIONS: These data indicate that the GS isolate OSA® stimulates insulin secretion from mouse and human islets in vitro, at least in part as a consequence of Ca(2+) influx and protein kinase activation.

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