Regulation of macrophage migration inhibitory factor (MIF) expression by glucose and insulin in adipocytes in vitro

Background: It has been reported that macrophage migration inhibitory facto r (MIF) stimulated insulin secretion from pancreatic islet beta-cells in an autocrine manner, which suggests its pivotal role in the glucose metabolis m. According to this finding, we evaluated MIF expression in cultured adipo cytes and epididymal fat pads of obese and diabetic rats to investigate its role in adipose tissue. Materials and Methods: The murine adipocyte cell line 3T3-L1 was used to ex amine MIF mRNA expression and production of MIP protein in response to vari ous concentrations of glucose and insulin. Epididymal fat pads of Otsuka Lo ng-Evans Tokushima fatty (OLETF) and Wistar fatty rats, animal models of ob esity and diabetes, were subjected to Northern blot analysis to determine M IF mRNA levels. Results: MIF mRNA of 3T3-L1 adipocytes was up-regulated by costimulation wi th glucose and insulin. Intra-cellular MIF content was significantly increa sed by stimulation, whereas its content in the culture medium was decreased . When the cells were treated with cytochalasin B, MIF secretion in the med ium was increased. Pioglitazone significantly increased MIF content in the culture medium of 3T3-L1 cells. However, MIF mRNA expression of both epidid ymal fat pads of OLETF and Wistar fatty rats was down-regulated despite a h igh plasma glucose level. The plasma MIF level of Wistar fatty rats was sig nificantly increased by treatment with pioglitazone. Conclusion: We show here that the intracellular glucose level is critical t o 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 p ositive regulator of insulin secretion. In this context, it is conceivable that MIF may affect the pathophysiology of obesity and diabetes.