Abstract
Objective: The aim of this study was to explore changes in serum levels and tissue expression of HGF and c-MET, and to determine how HGF/c-MET signaling contributes to the pathophysiology of GDM. Methods: A total of 44 pregnant women with normal glucose tolerance (NGT) and 32 pregnant women with GDM were studied. Blood samples were taken just before delivery, and placenta and visceral adipose tissue were taken immediately after cesarean delivery. Serum levels of HGF, soluble c-MET and insulin were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of HGF and c-MET was measured in the placenta and visceral adipose tissue. In addition, we investigated pregnancy of high fat diet (HFD) mice as an animal model of GDM. The glucose tolerance test (GTT) was performed at GD 10, and measured the serum levels of Hgf and soluble c-Met at GD 16. After scarifying mice, we measured the weight and expression of mRNA of Hgf and c-Met in WAT, placenta, liver and muscle. Results: Serum soluble c-MET levels were significantly higher in the GDM group (p <0.001). In multiple logistic regression analysis, soluble serum c-MET level was strongly associated with GDM (OR 9.063, p=0.027). There were more patients with increased mRNA expression of HGF and c-MET in placenta. Interestingly, the protein expression of HGF and c-MET in maternal visceral fat tissue was significantly higher in the GDM group. In mouse study, maternal serum levels of soluble c-Met in pregnant HFD (PH) mice were higher than in non-pregnant HFD (NPH) mice and pregnant chow diet (PC) mice. Relative mRNA expression of Hgf was significantly increased in eWAT of PH than PC mice. Relative c-Met mRNA expression was significantly increased in sWAT of PH than PC mice. Conclusion: We observed the differences in serum levels and expression of HGF and c-MET between GDM and control pregnant women in human and mice model. Our results suggest that HGF/c-MET signaling may be altered in GDM, which associated with insulin resistance and pathophysiology in GDM. Disclosure H.Kim: None. J.Lee: None. Y.Jung: None. M.Lee: None. J.Kim: None. K.Joung: None. B.Ku: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Sanofi, Novo Nordisk, LG Chem. Funding National Research Foundation of Korea (2022R1F1A1074608)
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