In vitro modulation of pancreatic insulin secretion, extrapancreatic insulin action and peptide glycation by Curcuma longa aqueous extracts

Abstract

Objective: Medicinal, edible, and aromatic plants have been used as folk remedies in traditional treatments worldwide. This study investigates the antidiabetic efficacy and action mode of Curcuma longa Linn. (Zingiberaceae). Methods: Effects of aqueous extracts (AEs) of C. longa on insulin secretion and action were studied using the insulin-secreting BRIN-BD11 and the adipocyte-like 3T3-L1 cell lines, respectively. In vitro models were employed to evaluate effects on starch digestion using α-amylase/amyloglucosidase and protein glycation. Results: C. longa AEs stimulated basal insulin output and potentiated glucose-stimulated insulin secretion concentration-dependently in the clonal pancreatic beta cell line, BRIN-BD11 (P < 0.001). The insulin secretory activity of plant extract was abolished in the absence of extracellular Ca 2+ and by inhibitors of cellular Ca 2+ uptake, diazoxide and verapamil (P < 0.001). Furthermore, the extract increased insulin secretion in depolarized cells and augmented insulin secretion triggered by 3-isobutyl-1-methylxanthine, tolbutamide, and glibenclamide. C. longa AEs lacked insulin mimetic activity but enhanced insulin-stimulated glucose transport in 3T3-L1 adipocytes by 370% (P < 0.001). Similar to aminoguanidine, C. longa AEs (1-50 mg/ml) effected concentration-dependent inhibition of protein glycation (24-70% inhibition, P < 0.001) in vitro. In bioassays of enzymatic starch digestion, C. longa AEs lacked inhibitory effects on α-amylase and α-glucosidase, unlike acarbose, the classical reference drug. Conclusion: This study has revealed that water soluble bioactive principles in C. longa AEs stimulate basal- and potentiate glucose evoked-insulin secretion, enhance insulin action and inhibit insulin glycation, but not starch digestion. Future work assessing the use of C. longa AEs as dietary adjunct or as a source of active antidiabetic agents may provide new opportunities for the combinatorial treatment/prevention of diabetes.