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Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice.
Journal of Endocrinology
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced by many cells and tissues including pancreatic beta-cells, liver, skeletal muscle, and adipocytes. This study investigates the potential role of MIF in carbohydrate homeostasis in a physiological setting outside of severe inflammation, utilizing Mif knockout (MIF-/-) mice. Compared with wild-type (WT) mice, MIF-/- mice had a lower body weight, from birth until 4 months of age, but subsequently gained weight faster, resulting in a higher body weight at 12 months of age. The lower weight in young mice was related to a higher energy expenditure, and the higher weight in older mice was related to an increased food intake and a higher fat mass. Fasting blood insulin level was higher in MIF-/- mice compared with WT mice at any age. After i.p. glucose injection, the elevation of blood insulin level was higher in MIF-/- mice compared with WT mice, at 2 months of age, but was lower in 12-month-old MIF-/- mice. As a result, the glucose clearance during intraperitoneal glucose tolerance tests was higher in MIF-/- mice compared with WT mice until 4 months of age, and was lower in 12-month-old MIF-/- mice. Insulin resistance was estimated (euglycemic-hyperinsulinemic clamp tests), and the phosphorylation activity of AKT was similar in MIF-/- mice and WT mice. In conclusion, this mouse model provides evidence for the role of MIF in the control of glucose homeostasis.
Age Factors, Analysis of Variance, Animals, Blood Glucose/metabolism, Blotting, Western, Body Composition/physiology, Body Weight/physiology, Energy Metabolism/physiology, Glucose Clamp Technique, Glucose Tolerance Test, Homeostasis/physiology, Insulin/metabolism, Insulin Resistance/physiology, Leptin/blood, Lipids/blood, Macrophage Migration-Inhibitory Factors/genetics, Macrophage Migration-Inhibitory Factors/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Activity/physiology, Reverse Transcriptase Polymerase Chain Reaction, Statistics, Nonparametric
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