| Gestational diabetes mellitus (GDM) is a frequent complication of pregnancies and is one of the leading causes of maternal and neonatal mortality and morbidity worldwide.Human pregnancy is characterized by insulin resistance, traditionally attributed to the effects of placental hormones. However, the pathogenetic mechanisms of further enhanced normal pregnancy-induced insulin resistance in GDM are not fully understood. The discovery that some adipokines were key players in the regulation of insulin action suggested possible roles of the placenta and adipose tissue in understanding pregnancy-induced insulin resistance. Visfatin, which was known as PBEF (pre-B-cell colony-enhancing factor), Nampt (nicotinamide phosphoribosyltransferase) and a new adipokine in visceral fat with insulin-mimetic effects, has drawn considerable interest in several fields, including NAD (nicotinamide adenine dinucleotide) biology, metabolism and inflammation.But the correlation between visfatin and GDM remains largely unknown. To further elucidate the main source of circulating visfatin during pregnancy and the potential roles of visfatin in pathogenesis of GDM, we examined serum levels and local concentrations of visfatin in subcutaneous adipose tissue(SAT), viscerl fat tissue(VAT)and placenta both in women with GDM and healthy pegnancy controls at term. Moreover, we also investigated if TNF-a regulate visfatin expression in Be Wo cells.Section 1 Serum visfatin levels of the normal pregnancy controls and women with GDMObjective:To investigate the changes of serum visfatin levels in women with gestational diabetes mellitus (GDM) and it association with GDM.Methods:Samples for measurement were obtained from 20 women with GDM and 22 normal pregnant controls at term. Serum visfatin levels before and three days after delivery as well as fetal serum visfatin levels were detected by ELISA. The HOMA-insulin resistance index (HOMA-IR) was calculated based on fasting plasma glucose (FPG) and fasting blood insulin (FIN S) with the minimal model.Results:1) Women with GDM showed significantly higher 1hPG, FINS, HOMA-IR and TNF-a than normal pregnant controls.2) Fasting serum visfatin levels were significantly higher in women with GDM than normal pregnant controls at term (7.9±2.0 vs.6.2±1.4ng/ml,P=0.004).Three days after delivery, serum visfatin levels obviously descent in GDM women than antepartum (7.9±2.0vs.6.3±1.7ng/ml, p=0.025). However, the changes in normal pregnancy women were not significant. There was no significant difference between fetal visfatin serum levels of the two groups. Fetal visfatin serum levels correlated positively with birth weight(r=0.513, p=0.001).3) In the whole group studied, serum visfatin level correlated positively with lh plasma glucose after glucose loading (lhPG, r=0.432, p=0.004). Data from multivariate analysis showed that visfatin (B=0.827,p=0.011, OR=2.287, 95%CI1.213～4.311) and FINS (B=0.416,p=0.031, OR=1.517,95%CI1.039～2.213) were independent predictors of GDM after further correcting 1hPG.Conclusions:Serum visfatin levels were significantly higher in women with GDM than normal pregnant controls at term, which is the significant independent predictor of insulin resistance. Visfatin may function as an inflammatory factor to contribute to the pathogenesis of GDM.Section 2 Visfatin expression in placenta, VAT and SATObjective:We aimed to evaluate the expression and localization of visfatin in human subcutaneous adipose tissue (SAT), visceral (omental) adipose tissue (VAT) and placental tissue from women with GDM and healthy pregnant controls in order to investigate the relationship between the expression of visfatin indifferent tissues and GDM.Methods:Samples for measurement were obtained from 20 women with GDM and 22 healthy pregnant controls at term. mRNA, protein expression and localization of visfatin in SAT, VAT and placenta were investigated using RT-PCR, western blot and immunohistochemistry, respectively.Results:The expressions of visfatin mRNA and protein in placenta were significantly higher in GDM women than controls (p=0.014;p=0.006), which were significantly correlated positively with serum visfatin concentrations (r=0.512,p=0.015; r=0.819, p=0.046). But there was no difference in visfatin expression in adipose tissue between the two groups. An IHC of placenta, VAT and SAT demonstrated strong visfatin staining, particularly in the syncytiotrophoblasts.Conclusion:Visfatin expression from placenta was the main source of elevated serum visfatin concentrations of women with GDM. There was no relationship detected between visfatin of adipose tissue and GDM. Visfatin may play an important part in glucose transport from the maternal to the fetal circulation.Section 3 Effects of TNF-a on visfatin expression in trophoblastObjectives:Visfatin expression from placenta is the main source of elevated serum visfatin concentrations of women with GDM. This study aimes to investigate the expression of visfatin in trophoblast under the regulation of tumor necrosis factor-a (TNF-a).Methods:BeWo cells as human trophoblast models were treated for 24,48, and 72 h with TNF-a within, below, and above physiologic concentrations (0.1,10, 100ng/ml).Results:Extracellular visfatin protein was measured in culture medium collected from Be Wo cells showed a significant increase in a concentration-depended way after 48 h incubation with TNF-a. Interestingly, a decreased level of intracellular visfatin mRNA expression paralleling the increased extracellular visfatin protein was detected in our study. We also found that the changes in protein expression of visfatin intracellular also corresponded with the decreasing of mRNA expression although without reaching significance.Conclusions:Visfatin expression of placenta was under the regulation of TNF-a through a concentration-depended way. Distinct changes of visfatin expression intra and extra BeWo cells may be due to the different functions of visfatin in different location.Visfatin may through NAD biology, metabolism and inflammation way to contribute to the pathogenesis of GDM.
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