Endocrine Abstracts

Aim: Gallic acid is one of the major bioactive phenolic compounds that have been isolated from several plant extracts with reported antidiabetic actions. However, insulinotropic effects and mechanisms underlying antidiabetic actions of garlic acid is poorly understood. This study investigated insulin-releasing and glucose-lowering effects of gallic acid.

Methods: Glucose-stimulated insulin secretion in BRIN-BD11 cells were examined in the absence or presence of graded concentrations of gallic acid or in combination with modulators of insulin secretion. Cytotoxic effects in cells and effects of garlic acid on glucose tolerance in mice with diet-induced obesity-diabetes were also examined.

Results: Gallic acid (0-10µM) stimulated significant (P < 0.01 -0.001) and non-toxic dose-dependent secretion of insulin release from BRIN-BD11 cells with the highest stimulatory effect (2.1-fold, P < 0.001) at 10µM. Chronic (24 h) exposure of BRIN-BD11 cells to gallic acid produced enhanced insulin secretion (0-10 µM, 1.2- to 1.5-fold, P < 0.001-0.05). Insulin-release stimulatory actions of gallic acid increased with increasing glucose concentration (1.1mM to 5.6mM = 33%, P < 0.001; 5.6mM to 16.7mM = 11%, P < 0.01) and in the presence of stimulators (30mM KCl = 4.6-fold, P < 0.001; tolbutamide = 200µM, 2.4-fold, P < 0.01). Reduced effects were observed in incubations lacking calcium (44%, P < 0.01) and in the presence of verapamil (50nM, 31%, P < 0.01) and diazoxide (300µM, 27%, P < 0.01). Garlic acid increased intracellular calcium concentration (24%, P < 0.05) and membrane potential (20%, P < 0.05) in BRIN-BD11 cells as well as glucose tolerance (22%, P < 0.05) and plasma insulin (23%, P < 0.05) in high fat-fed mice.

Conclusion: These results encourage the investigation of long-term effects of garlic acid in animal models of type 2 diabetes.