Macrophage migration inhibitory factor is a therapeutic target in treatment of non-insulin-dependent diabetes mellitus

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in the pathogenesis of a variety of autoimmune inflammatory diseases. Here, we investigated the role of MIF in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) using MIF−/− mice and a mouse model of streptozotocin (STZ)-induced NIDDM. Following single injection of STZ, MIF+/+ BALB/c mice showed a significant increase in blood glucose levels, developed polyuria, and succumbed to disease. In contrast, no such increase in blood glucose was observed in MIF−/− BALB/c mice treated with STZ. These mice produced significantly less inflammatory cytokines and resistin as compared with MIF+/+ mice and failed to develop clinical disease. Finally, oral administration of a small-molecule MIF antagonist, CPSI-1306, to outbred ICR mice following induction of NIDDM significantly lowered blood glucose levels in the majority of animals, which was also associated with a significant reduction in the levels of the proinflamma...