en
Scientific article
English

Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice

Published inJournal of Endocrinology, vol. 206, no. 3, p. 297-306
Publication date2010
Abstract

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.

Keywords
  • 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/ metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity/physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric
Citation (ISO format)
SERRE-BEINIER, Veronique et al. Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice. In: Journal of Endocrinology, 2010, vol. 206, n° 3, p. 297–306. doi: 10.1677/JOE-09-0342
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Identifiers
ISSN of the journal0022-0795
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