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To determine whether extracts of Gymnema sylvestre may have therapeutic potential for the treatment of noninsulin-dependent diabetes mellitus (NIDDM), we examined the effects of an alcoholic extract of G. sylvestre (GS4) on insulin secretion from rat islets of Langerhans and several pancreatic -cell lines. GS4 stimulated insulin release from HIT-T15, MIN6 and RINm5F -cells and from islets in the absence of any other stimulus, and GS4-stimulated insulin secretion was inhibited in the presence of 1 mM EGTA. Blockade of voltage-operated Ca 2+ channels with 10 µM isradipine did not significantly affect GS4-induced secretion, and insulin release in response to GS4 was independent of incubation temperature. Examination of islet and -cell integrity after exposure to GS4, by trypan blue exclusion, indicated that concentrations of GS4 that stimulated insulin secretion also caused increased uptake of dye. Two gymnemic acidenriched fractions of GS4, obtained by size exclusion and silica gel chromatography, also caused increases in insulin secretion concomitant with increased trypan blue uptake. These results confirm the stimulatory effects of G. sylvestre on insulin release, but indicate that GS4 acts by increasing cell permeability, rather than by stimulating exocytosis by regulated pathways. Thus the suitability of GS4 as a potential novel treatment for NIDDM can not be assessed by direct measurements of -cell function in vitro.

The potential role of oestrogenic agents, antioxidants and intestinal glucose‐uptake inhibitors in the treatment of diabetes is briefly reviewed. Reports in the literature suggest that oestrogen replacement therapy may favourably modulate glucose homeostasis. A soya phytochemical extract (SPE) containing the isoflavone phytoestrogens genistein and daidzein (mostly in their glycone forms as genistin and daidzin) was investigated as an antioxidant and modulator of intestinal glucose‐transport. In the present study, SPE was found to protect against glucose‐induced oxidation of human low density lipoproteins (LDL) in vitro. Equol (a gut bacterial metabolite of daidzein) was a more effective antioxidant than daidzein or genistein in this system and was of similar antioxidant potency to the dietary flavonols quercetin and kaempferol and to the endogenous antioxidant 17β‐oestradiol. SPE was found to be an inhibitor of glucose uptake into rabbit intestinal brush border membrane vesicles in vitro, though of weaker potency than the classical sodium dependent glucose transporter (SGLT) inhibitor, phlorizin. Thus SPE displays a range of properties which may be of benefit in diabetes, namely as an oestrogenic agent, an inhibitor of intestinal glucose‐uptake and a preventive agent for glucose‐induced lipid peroxidation. Copyright © 1999 John Wiley & Sons, Ltd.