Gymnema sylvestre Extracts Stimulate Insulin Secretion In vitro and In vivo: a Potential Phytopharmacological Therapy for Type 2 Diabetes
Abstract Number: 2243-PO
Authors: PETER M. JONES, C R. MAITY, S K. CHATTERJEE, N KOLEY, H ASARE-ANANE, T BISWAS, K ROY, S J. PERSAUD, ARUN K. CHATTERJI, London, United Kingdom, Calcutta, India, Neenah, WI
Results: Plant-derived extracts have been used to treat Type 2 diabetes mellitus (T2DM) for several millennia, and the Santals in east-central India have used Gymnema sylvestre leaves as a folk-medicine for centuries. We have now investigated the potential anti-diabetogenic effects of an ayurvedically prepared Gymnema sylvestre virgin isolate extract (designated OSA for Om Santal Adivasi; U.S. Patents # 6,949,261, # 6,946,151). In vitro studies using human islets and the insulin-secreting MIN6 cell line demonstrated that OSA (0.06-2mg/ml) induced a concentration-dependent stimulation of insulin secretion (0.5mg/ml OSA: 745±71% and 807±84% 2mM and 20mM glucose-stimulated secretion respectively, n=10, p<0.001). OSA-induced insulin secretion was rapidly reversible on removal of OSA, and was at least partially dependent on an influx of extracellular calcium (0.2mg/ml OSA: 368±32% 2mM glucose response; 237±22% in absence of calcium, n=6, p<0.05). Clinical studies in non-obese patients with T2DM confirmed the insulin-releasing effect of OSA. Thus, daily ingestion of OSA (1000mg/day) for 60 days resulted in significant elevations in basal serum levels of insulin (24.3±2.8 vs 32.1±1.9mU/L, n=11, p<0.01) and C-peptide (298±42pM vs 448±48, p<0.01). The increased circulating insulin after OSA treatment was accompanied by significant reductions in fasting blood glucose (9.8±0.5mM vs 7.6±0.53, n=14, p<0.01), and by reductions in the post-prandial glucose excursions (16.1±1.1mM vs 13.6±1.1, p<0.01). OSA treatment also reduced cholesterol by 13% and triglycerides by 26%. These clinical data suggest that OSA may offer an effective therapy for insulin-deficient T2DM. Moreover, the in vitro studies suggest that at least one mechanism of action of OSA is in directly stimulating insulin secretion. OSA may therefore offer a safe sole therapy for T2DM or an adjunct to conventional oral hypoglycemic drugs.