Abstract
AIM: Abrus precatorius leaves methanolic extract (APME) was evaluated for in vivo antihyperglycemic activity and in vitro insulinotropic effect. MATERIALS AND METHODS: In vivo antihyperglycemic and insulin secretagogue activities were assessed in streptozotocin-induced diabetic rats by oral administration of APME (200 mg/kg body weight [bw]) for 28 days. In vitro insulin secretion mechanisms were studied using mouse insulinoma beta cells (MIN6-β). In vivo body weight and blood glucose and in vivo and in vitro insulin levels were estimated. RESULTS: In diabetic rats, APME treatment significantly restored body weight (26.39%), blood glucose (32.39%), and insulin levels (73.95%) in comparison to diabetic control rats. In MIN6-β cells, APME potentiated insulin secretion in a dependent manner of glucose (3-16.7 mM) and extract (5-500 μg/mL) concentration. Insulin secretagogue effect was demonstrated in the presence of 3-isobutyl-1-methyl xanthine, glibenclamide, elevated extracellular calcium, and K(+) depolarized media. Insulin release was reduced in the presence of nifedipine, ethylene glycol tetra acetic acid (calcium blocking agents), and diazoxide (potassium channel opener). CONCLUSION: The study suggests that APME antihyperglycemic activity might involve the insulin secretagogue effect by pancreatic beta cells physiological pathways via K(+)-ATP channel dependent and independently, along with an effect on Ca(2+) channels. SUMMARY: Abrus precatorius leaves methanolic extract (APME) showed a significant anti hyperglycemic and insulin secretagogue activities in streptozotocin induced diabetic rats. Also demonstrated a potent In vitro insulin secretagogue effect in mouse insulinoma beta cells (MIN6-β)APME treatment significantly restored body weight (26.39%), reduced blood glucose (32.39%) and enhanced circulatory insulin levels (73.95%) in diabetic ratsAPME demonstrated glucose and extract dose dependent insulin secretionInsulin secretagogue effect was demonstrated in the presence of 3-isobutyl-1-methyl xanthine, glibenclamide, elevated extracellular calcium and K+ depolarized media. Insulin release was reduced in the presence of nifedipine and ethylene glycol tetra acetic acid (Calcium blocking agents), diazoxide (potassium channel opener)The insulinotropic effect of APME involves a physiologic effect on K+-ATP channel and Ca(2+) channels Abbreviations Used: ANOVA: Analysis of variance, CMC: Carboxy methyl cellulose, cAMP: Cyclic adenosine monophosphate, CaCl: Calcium chloride, AP: Abrus precatorius, APME: Abrus precatorius methanolic extract, DMEM: Dulbecco's modified Eagle's medium, DMSO: Dimethyl sulphoxide, EGTA: Ethylene glycol tetra acetic acid, FCS: Fetal calf serum, IBMX: 3-Isobutyl-1-methylxanthine, KCl: Potassium chloride, KRB: Kreb's Ringer buffer, MIN6: Mouse insulinoma cell line, MTT: 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide, STZ: Streptozotocin.