Antidiabetic effect of Carissa carandas in rats and the possible mechanism of its insulin secretagogues activity in isolated pancreatic islets
Carissa carandas (CC) has been used in folklore medicine for treatment of diabetes. In the present study, hexane, chloroform, ethyl acetate, methanol and aqueous extracts of CC fruit were examined for hypoglycemic activity in healthy Wistar rats. Aqueous Extract of CC (AECC) was most active and showed fall of 67.08% in fasting blood glucose from 0 to 1h in glucose tolerance test (GTT). The ED50 of AECC was 300mg/kgbw in streptozotocin induced diabetic rats. Treatment of diabetic rats with ED50 of AECC for 28 days significantly reduced post prandial glucose (PPG) by 33.65% (p<0.01), glycosylated hemoglobin (HbA1c) by 45.79% (p<0.01) and increased insulin level by 69.7% (p<0.05). The results indicated that increase in insulin secretion may be partly responsible for antidiabetic effect of AECC. To assess the mechanism of secretagogues activity, AECC was incubated with isolated pancreatic islets of healthy Wistar rats at basal (3.3mM) and high (16.7mM) level of glucose in presence or absence of Diazoxide (K-ATP channel opener), Nimodipine (Ca2+ Channel blocker) and Calphostin-C (PKC inhibitor). AECC induced insulin secretion at 16.7mM of glucose was significantly (p<0.01) reduced by Diazoxide and Nimodipine but non significantly (p>0.05) by Calphostin-C. The study indicated that the phytochemicals present in AECC may be inducing insulin secretion by closing K-ATP channels in β-cells of pancreatic islets.