Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice
Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice
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DOI：
10.1677/joe-09-0342
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
Berney, Thierry
中科院分区：
文献类型：
--
作者：
Serre-Beinier, Veronique;Toso, Christian;Berney, Thierry
巨噬细胞迁移抑制因子 (MIF) 是一种促炎细胞因子，由许多细胞和组织产生，包括胰腺 β 细胞、肝脏、骨骼肌和脂肪细胞。本研究利用 Mifknockout (MIF-/-) 小鼠，研究了 MIF 在严重炎症之外的生理环境中碳水化合物稳态中的潜在作用。与野生型（WT）小鼠相比，MIF-/-小鼠从出生到4个月大的体重较低，但随后体重增加得更快，导致12个月大时体重较高。年轻小鼠的较低体重与较高的能量消耗有关，而年老小鼠的较高体重与食物摄入量的增加和较高的脂肪量有关。与任何年龄的WT小鼠相比，MIF-/-小鼠的空腹血胰岛素水平较高。 ip 之后葡萄糖注射后，2月龄时MIF-/-小鼠的血液胰岛素水平较WT小鼠更高，但12月龄的MIF-/-小鼠的血液胰岛素水平较低。结果，在腹膜内葡萄糖耐量试验期间，与WT小鼠相比，MIF-/-小鼠在4个月龄之前的葡萄糖清除率较高，而在12个月大的MIF-/-小鼠中则较低。评估了胰岛素抵抗（正常血糖-高胰岛素钳夹试验），并且 MIF-/- 小鼠和 WT 小鼠中 AKT 的磷酸化活性相似。总之，该小鼠模型为 MIF 在控制葡萄糖稳态中的作用提供了证据。内分泌学杂志 (2010) 206, 297-306
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 Mifknockout (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. Journal of Endocrinology (2010) 206, 297-306