Research Of The Relationship Between GDF15 And Abnormal Metabolism During Pregnancy And CMPF And Skeletal Muscle Insulin Resistance

BACKGROUNDThe first part investigated the relationship between human serum growth differentiation factor 15(GDF15)and metabolic abnormalities during pregnancy.With the rapid development of society and the continuous improvement of the quality of life,the incidence of metabolic diseases such as hyperglycemia,obesity and hypertension in pregnant women increases continuously.It has been reported that serum growth differentiation factor 15(GDF15)is significantly increased in pregnant women.It is also closely related to glucose metabolism in people with diabetes,and studies in mice have found that GDF15 is also closely related to food intake and body weight.However,there are still few studies on the relationship between serum GDF15 and metabolic abnormalities during pregnancy.Therefore,the study on the relationship between serum GDF15 and metabolic abnormalities in pregnancy is expected to provide a new serum marker for the effective control of metabolic abnormalities in pregnant women and early warning during pregnancy.The second part is to study the relationship of 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid(CMPF)and insulin resistance in skeletal muscle cells.Insulin resistance mainly occurs in skeletal muscle,liver and adipose tissue.While studies have reported that CMPF can improve insulin resistance in liver tissue,but studies in skeletal muscle have not yet found it.Therefore,we want to investigate whether CMPF can also play a role in insulin resistance of skeletal muscle.METHODSPart I:We recruited 200 patients with gestational diabetes mellitus(GDM)and 211 pregnant women with normal glucose tolerance as controls at 24-28 weeks of gestation.The diagnosis of GDM was based on the guidelines issued by the World Health Organization in 2013.GDF15 levels of fasting serum of all subjects were determined by enzyme-linked immunosorbent assay(ELISA).Subjects were then divided into a normal metabolic group,an abnormal metabolic group,or two or more abnormal metabolic groups based on the number of metabolic abnormalities(including blood sugar,blood lipids,and blood pressure).Finally,multiple logistic regression analysis was used to estimate the odds ratio(OR)and 95%CIs ratio between GDF15 and metabolic abnormalities in pregnant women.Part II:C2C12 cells were induced to differentiate into skeletal muscle cells,and a skeletal muscle insulin resistance model was constructed treating by glucosamine.After3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid(CMPF)treatment,we detected the activation of insulin signaling pathway by western blot,to analyze the insulin resistance of skeletal muscle.RESULTSPart I:Through bivariate correlation analysis,we found that serum GDF15 is linearly correlated with glucose metabolism indices,such as lh-PG,2h-PG,HbAlc(all p<0.05).In addition,serum GDF15 and triglycerides were linearly correlated(p<0.05).Grouping by number of metabolic abnormalities,we found that as GDF15 levels increased,the risk of metabolic abnormalities also increased(OR>1),and the risk of multiple metabolic abnormalities was higher.As the number of metabolic abnormalities increased,serum GDF15 levels also were elevated(p<0.001).Part II:AfterC2C12 cells differentiation into skeletal muscle cells,glucosamine and CMPF were added,and it was found that CMPF can prevent glucosamine-induced skeletal muscle insulin resistanceCONCLUSION(1)The serum GDF15 levels are closely associated with metabolic abnormalities in pregnant women and may be used as a predictor of metabolic abnormalities during pregnancy.(2)CMPF can prevent insulin resistance of skeletal muscle induced by glucosamine.