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Endocrine Abstracts (2005) 10 DP1

SFE2005 Poster Presentations (1) Diabetes, metabolism and cardiovascular (12 abstracts)

Stimulation of insulin secretion by an aqueous extract of Gymnema sylvestre: role of intracellular calcium

H Asare-Anane , GC Huang , SA Amiel , PM Jones & SJ Persaud


King’s College, London, United Kingdom.


Objective

Plant-derived extracts have long been used to treat Type 2 diabetes mellitus (T2DM), but their effects have not been rigorously investigated at the cellular level in vitro. The aims of the current study were to determine the effects of a virgin isolate of Gymnema sylvestre (GS), designated OSA, on pancreatic β-cell function.

Materials and Methods

Cell viability was measured by Trypan blue exclusion tests, [Ca2+]i was determined by single cell microfluorimetry and insulin secretion was measured by radioimmunoassay.

Results

OSA (0.06–2 mg/ml) caused a dose-dependent increase in insulin secretion from MIN6 insulin-secreting cells at both 2mM and 20mM glucose, with statistically significant (P<0.05) effects at ≥0.125 mg/ml. Concentrations of OSA≥0.5 mg/ml decreased cell viability, as assessed by an increase in cellular Trypan blue uptake, so all future experiments were performed with 0.125 mg/ml OSA. The stimulatory effects of OSA on insulin secretion were significantly reduced in the absence of extracellular Ca2+, indicating that at least part of the effect of OSA was dependent on Ca2+ influx. OSA (0.125 mg/ml) stimulated a rapid, transient and reversible elevation in [Ca2+]i in Fura 2-loaded MIN6 cells. OSA significantly stimulated insulin secretion from isolated human islets of Langerhans in perifusion experiments. It caused a rapid increase in insulin secretion at 2mM glucose (peak: 266±54% basal; plateau: 166±12% basal, n=3), and this was readily reversible indicating that insulin release was not secondary to membrane damage. 0.125 mg/ml OSA also potentiated insulin secretion from human islets at 20 mM glucose (rapid 4.4-fold increase over the 20 mM glucose-induced plateau phase).

Conclusions

OSA, a water-soluble extract of GS, caused reversible increases in intracellular calcium and insulin secretion in mouse and human β-cells when used at a concentration (0.125 mg/ml) that did not compromise cell viability. These data suggest that extracts derived from GS may be useful as therapeutic agents for the stimulation of insulin secretion in individuals with T2DM.

Volume 10

196th Meeting of the Society for Endocrinology and Society for Endocrinology joint Endocrinology and Diabetes Day

Society for Endocrinology 

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