Increased ambient glucose concentrations enhanced the expressions of S100A8/A9 in co-cultured islets with macrophages. Isolated pancreatic islets (200 islets for A and B, 50 islets for C and D) were co-cultured with peritoneal macrophages (5 × 105 cells for A and B, 1 × 105 cells for C and D) in medium containing BSA in the presence/absence of palmitate. A, isolated islets were co-cultured with macrophages in the presence of 5.6 or 11.1 mmol/liter of glucose with/without palmitate for 48 h. Total cell extracts from the islets were subjected to immunoblotting as indicated. B, secreted S100A8 protein levels in the supernatant from a co-culture of islets with macrophages in the presence/absence of palmitate and 5.6 or 11.1 mmol/liter glucose for 48 h. Horizontal bars, mean values. n.s., not significant; **, p ≤ 0.01 (n = 3). C, mRNA expression levels in islets co-cultured with macrophages in the presence of 5.6 or 11.1 mmol/liter glucose with/without palmitate for 24 h. Horizontal bars, mean values. **, p ≤ 0.01 (n = 6). D, mRNA expression levels in macrophages co-cultured with islets in the presence of 5.6 or 11.1 mmol/liter glucose with/without palmitate for 24 h. Horizontal bars, mean values. *, p ≤ 0.05; **, p ≤ 0.01 (n = 6).