title: Macrophage migration inhibitory factor is a therapeutic target in treatment of non-insulin-dependent diabetes mellitus.
abstract: 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.
authors.affiliation: Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Sanchez-Zamora
authors.forename: Luis I
authors.initials: LI
authors.lastname: Terrazas
authors.forename: Alonso
authors.initials: A
authors.lastname: Vilches-Flores
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Leal
authors.forename: Imelda
authors.initials: I
authors.lastname: Juárez
authors.forename: Caroline
authors.initials: C
authors.lastname: Whitacre
authors.forename: Aaron
authors.initials: A
authors.lastname: Kithcart
authors.forename: James
authors.initials: J
authors.lastname: Pruitt
authors.forename: Thais
authors.initials: T
authors.lastname: Sielecki
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
authors.forename: Miriam
authors.initials: M
authors.lastname: Rodriguez-Sosa
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D015850:Interleukin-6 / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001786:Blood Glucose; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha