Enhanced Release of Monocyte Chemoattractant Protein-1 (MCP-1) by High Glucose and Free Fatty Acid and its Underlying Mechanism in MIN6 β cells

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Monocyte chemoattractant protein (MCP)-1, a member of the C-C chemokine family, is released from pancreatic β cells, and numerous macrophages have been shown to be infiltrated in pancreatic islets of type 2 diabetic rats. We investigated changes in MCP-1 release from MIN6 β cells under the condition of glucolipotoxicity and the underlying mechanism. The incubation of the cells with 25 mmol/L glucose and 0.3 mmol/L palmitic acid for 6 h and 24 h significantly increased MCP-1 release compared to control cells incubated with 5.6 mmol/L glucose (p < 0.01). Increased MCP-1 secretion from MIN6 β cells incubated for 24 h with high glucose and palmitic acid was found to be significantly suppressed by the addition of antioxidant N-acetylcysteine (p < 0.01). In addition, the IκB phosphorylation inhibitor BAY 11-7085 significantly inhibited MCP-1 secretion in a dose-dependent manner (p < 0.05-0.01) while a JNK inhibitor SP 600125 did not show any significant effect. Enhanced oxidative stress is thought to be a causative factor for upregulation of MCP-1 release from β cells under high glucose/palmitic acid condition. The IκB-α/nuclear factor-κB (NF-κB)-dependent pathway might be predominantly important for this upregulation.