| First Author | Sanchez-Zamora Y | Year | 2010 |
| Journal | FASEB J | Volume | 24 |
| Issue | 7 | Pages | 2583-90 |
| PubMed ID | 20203087 | Mgi Jnum | J:162358 |
| Mgi Id | MGI:4818746 | Doi | 10.1096/fj.09-147066 |
| Citation | Sanchez-Zamora Y, et al. (2010) Macrophage migration inhibitory factor is a therapeutic target in treatment of non-insulin-dependent diabetes mellitus. FASEB J 24(7):2583-90 |
| abstractText | 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 proinflammatory cytokines IL-6 and TNF-alpha in the sera. Taken together, these results demonstrate that MIF is involved in the pathogenesis of NIDDM and is a therapeutic target to treat this disease. |
