These factors can activate toll-like receptor (TLR) signaling both in beta cells and macrophages by elevating circulating levels of TLR ligands, triggering signaling pathways driven by NFκB and STAT1, which consequently decrease beta cell insulin gene expression and secretion, and highlights the important role macrophage activation may play in the initiation and progression of insulitis in diabetes (34, 50, 60). The gene discussed is INS; the disease is diabetes mellitus.