Regulation of Macrophage Migration Inhibitory Factor (MIF) Expression by Glucose and Insulin in Adipocytes In Vitro

Abstract

Background: It has been reported that macrophage migration inhibitory factor (MIF) stimulated insulin secretion from pancreatic islet (3-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. Materials and Methods: The murine adipocyte cell line 3T3-Ll 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. Results: MIF mRNA of 3T3-L1 adipocytes was up-regulated by costimulation with glucose and insulin. Intra-cellular 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. Conclusion: We show here that the intracellular glucose level is critical to determining the MWP mnRNA 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.

Systemic Immune Mediators and Lifestyle Changes in the Prevention of Type 2 Diabetes

“…Moreover, MIF acts as an autocrine factor promoting insulin production and release. MIF production is stimulated by high glucose concentrations, whereas neutralization of MIF or inhibition of MIF gene expression impaired glucose-induced insulin secretion (31)(32)(33). Taken together, high MIF levels may promote ␤-cell function.…”

Obesity, macrophage migration inhibitory factor, and weight loss

“…1,8,9 MIF is produced and released by a number of tissues throughout the body, and in rodents, MIF is expressed and released from adipocites. 10 Excess body fat is associated with an increased risk of numerous morbidities including CVD, diabetes, and some cancers. 11 However, the pathophysiological mechanisms whereby increased body weight promotes these health conditions remains largely unexplained.…”

Inhibition of macrophage migration inhibitory factor (MIF) tautomerase and biological activities by acetaminophen metabolites

“…MIF has the capacity to override, or counterregulate, the immunosuppressive effects of glucocorticoids (5,6,8,10), which accounts in part for the proinflammatory role of MIF in conditions such as septic shock (5,6,(11)(12)(13), arthritis (14)(15)(16), and glomerulonephritis (17). Additional biological activities for MIF include the regulation of macrophage and T cell activation (7,8), IgE synthesis (18), insulin release (19) and carbohydrate metabolism (20,21), cell growth and apoptosis (22,23), and tumor angiogenesis (24).…”