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

Diabetes Obes Metab. 2012 Dec;14(12):1104-13. doi: 10.1111/j.1463-1326.2012.01660.x. Epub 2012 Aug 1.


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 KATP 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.

Keywords: beta cell; diabetes mellitus; insulin secretagogue; insulin secretion; islets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Line
  • Gymnema sylvestre*
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Intracellular Calcium-Sensing Proteins / drug effects
  • Intracellular Calcium-Sensing Proteins / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Mice
  • Phytotherapy / methods
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Preparations / chemistry
  • Plant Preparations / pharmacology*
  • Protein Kinases / drug effects
  • Protein Kinases / metabolism*


  • Insulin
  • Intracellular Calcium-Sensing Proteins
  • Plant Extracts
  • Plant Preparations
  • Protein Kinases
  • Calcium