Activation of GPR40 by CNX-011-67 treatment reduces glucagon secretion. (A) Glucagon secretion was reduced under high glucose condition and was further reduced by CNX-011-67 treatment. After culturing islets under vehicle control (VC) or chronic glucolipotoxic (GL) conditions in presence or absence of CNX-011-67, islets were treated with high glucose concentration for 2 h and amount of secreted glucagon (B), islet glucagon content (C) and glucagon secretion as % of content (D) were determined. After chronic culture, islets were used for gene expression analysis and mRNA levels of glucagon (GCG) (E) and GPR40 (F) were quantified. Data are represented as mean ± SEM from four replicates and statistical analyses were performed by ANOVA with Newman-Keuls post test (*P < 0.05, **P < 0.01 and ***P < 0.001).