Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice.
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.
Serre-Beinier
Véronique
V
Surgical Research Unit, Department of Surgery Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, 1211 Geneva 4, Switzerland. veronique.serre@unige.ch
Toso
Christian
C
Morel
Philippe
P
Gonelle-Gispert
Carmen
C
Veyrat-Durebex
Christelle
C
Rohner-Jeanrenaud
Françoise
F
Calandra
Thierry
T
Roger
Thierry
T
James
Richard W
RW
Montet
Xavier
X
Bühler
Léo
L
Bosco
Domenico
D
Berney
Thierry
T
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids; D008263:Macrophage Migration-Inhibitory Factors