Proglucagon gene expression in microglia is decreased by the free fatty acid palmitate. Microglia were exposed to 0.125 mM palmitate for 24 h. A. Proglucagon gene expression is significantly reduced in microglia exposed to palmitate (mimicking the diabetic milieu in vitro). B. GLP-1 secretion is not significantly reduced after treatment of microglia with palmitate. GLP-1 secretion was measured as pM and presented as percent of control. C. No significant effect on TNFα secretion is detected after a 2-h exposure to palmitate; however, TNFα secretion is reduced from microglia treated with palmitate for 24 h. TNFα secretion was measured as pg/ml and presented as percent of control. D. TNFα expression is significantly reduced in microglia exposed to palmitate. E. Treatment with palmitate increases the expression of chitinase-3 and arginase 1. F. Treatment with LPS decreases the expression of arginase 1 after 24 h. mRNA expression was calculated after normalizing to mRNA expression of GAPDH, used as an internal control. Bars represent mean ± SEM, n = 3, in triplicates. * and **P < 0.05 and P < 0.001, respectively, for chance differences vs. untreated controls. Statistical analysis was performed using Mann-Whitney rank sum test and Student’s t-test (C,D).