Sakaue S, Nishihira J, Hirokawa J, Yoshimura H, Honda T, Aoki K, Tagami S, Kawakami Y
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Mol Med. 1999 Jun;5(6):361-71.
It has been reported that macrophage migration inhibitory factor (MIF) stimulated insulin secretion from pancreatic islet beta-cells in an autocrine manner, which suggests its pivotal role in the glucose metabolism. According to this finding, we evaluated MIF expression in cultured adipocytes and epididymal fat pads of obese and diabetic rats to investigate its role in adipose tissue.
The murine adipocyte cell line 3T3-L1 was used to examine MIF mRNA expression and production of MIF protein in response to various concentrations of glucose and insulin. Epididymal fat pads of Otsuka Long-Evans Tokushima fatty (OLETF) and Wistar fatty rats, animal models of obesity and diabetes, were subjected to Northern blot analysis to determine MIF mRNA levels.
MIF mRNA of 3T3-L1 adipocytes was up-regulated by costimulation with glucose and insulin. Intracellular MIF content was significantly increased by stimulation, whereas its content in the culture medium was decreased. When the cells were treated with cytochalasin B, MIF secretion in the medium was increased. Pioglitazone significantly increased MIF content in the culture medium of 3T3-L1 cells. However, MIF mRNA expression of both epididymal fat pads of OLETF and Wistar fatty rats was down-regulated despite a high plasma glucose level. The plasma MIF level of Wistar fatty rats was significantly increased by treatment with pioglitazone.
We show here that the intracellular glucose level is critical to determining the MIF mRNA level as well as its protein content in adipose tissue. MIF is known to play an important role in glucose metabolism as a positive regulator of insulin secretion. In this context, it is conceivable that MIF may affect the pathophysiology of obesity and diabetes.
据报道，巨噬细胞移动抑制因子（MIF）以自分泌方式刺激胰岛β细胞分泌胰岛素，这表明其在葡萄糖代谢中起关键作用。基于这一发现，我们评估了肥胖和糖尿病大鼠培养的脂肪细胞及附睾脂肪垫中MIF的表达，以研究其在脂肪组织中的作用。
使用小鼠脂肪细胞系3T3-L1，检测其在不同浓度葡萄糖和胰岛素作用下MIF mRNA的表达及MIF蛋白的产生。对肥胖和糖尿病动物模型大耳白兔（OLETF）和Wistar肥胖大鼠的附睾脂肪垫进行Northern印迹分析，以确定MIF mRNA水平。
葡萄糖和胰岛素共同刺激可上调3T3-L1脂肪细胞的MIF mRNA表达。刺激后细胞内MIF含量显著增加，而培养基中的含量则降低。用细胞松弛素B处理细胞后，培养基中MIF的分泌增加。吡格列酮显著增加3T3-L1细胞培养基中的MIF含量。然而，尽管血浆葡萄糖水平较高，OLETF和Wistar肥胖大鼠附睾脂肪垫的MIF mRNA表达均下调。吡格列酮治疗可使Wistar肥胖大鼠的血浆MIF水平显著升高。
我们在此表明，细胞内葡萄糖水平对于确定脂肪组织中MIF mRNA水平及其蛋白含量至关重要。已知MIF作为胰岛素分泌的正调节因子在葡萄糖代谢中起重要作用。在这种情况下，可以想象MIF可能影响肥胖和糖尿病的病理生理过程。
