TLR4 and Hyperglycemia: In cultured macrophages, the intermittent episodes of hypoglycemia and hyperglycemia (3–15 mmol/L) promoted M1 polarization and an inflammatory response, estimated by the secretion of integrin alpha X, IL-1β, TNF-α, IL-6 and MCP-1, via a mechanism involving the Toll-like receptor 4 (TLR4)–interferon regulatory factor 5 (IRF5) pathway [45].