Correlation Between Serum Ferritin And Insulin Resistance In Gestational Diabetes During Different Pregnancy

Objective:To investigate the correlation between serum ferritin and insulin resistance and the expression of some signaling factors in the insulin receptor IRS1-PI3K-AKT pathway during pregnancy in gestational diabetes rats,and to explore the possible interaction between serum ferritin and insulin resistance,and to infer serum ferritin The relationship with the pathogenesis of gestational diabetes causes people to pay attention to the high-iron status during pregnancy or the potential harmfulness of iron supplementation.It advocates clinicians to selectively iron the pregnant women with gestational diabetes and provide new treatment for gestational diabetes.Methods:1.Establishment of rat model of gestational diabetes induced by rouge diet and acquisition of experimental tissueFifty-five 180-200g female Sprague-Dawley rats were randomly fed into the rouge diet group(HF group)and the low-fat diet group(NC group)for 25 weeks.The HF group was given rouge.For feed feeding,the NC group and the selected 9 male SD rats of 250-300 g were fed with normal diet.After HF group and NC group were reared for 3 months,the rats were not caged,7 days pregnant,14 days pregnant and 20 days pregnant.The rats were named as non-pregnant group,early pregnancy group,middle pregnancy group and late pregnancy.group.Weighing was measured regularly throughout the observation period and fasting insulin(FPG)was measured.The oral glu cose toleran ce test(OGTT)was performed one day before sacrifice and the area under the curve of blood glucose(AUG)was calculated.One day after the OGTT experiment,each group of rats was 0.3 ml.After an intraperitoneal injection of 10%chloral hydrate at a dose of 100 g,the serum and tissues of each group were sacrificed.The insulin insulin(FINS)and C-peptide levels were measured by ELISA kit,and the homeostasis model assessment(HOMA-IR)was calculated using homeostasis model assessment(HOMA).For:HOMA-IR=FPG×FINS/22.5,calculate the islet ?-cell index(HBCI)and insulin sensitivity index(homeostasis model assessment-insulin sensitivity,HOMA-IS)to determine the degree of insulin resistance.2.Determination of serum ferritin in gestational diabetes rats,expression of PI3K,IRS-1 in liver and correlation with insulin resistanceSerum ferritin(SF)levels were measured and the relationship between various parameters of pregnancy and serum ferritin was analyzed.Reverse transcription polymerase chain reaction(RT-PCR)and Western blotting were used to detect the mRNA and protein expression of PI3K and IRS1 in rat liver tissues,and the relationship with serum ferritin and insulin resistance was analyzed.Results:1.After one month of high-fat diet feeding,the body weight of HF group was significantly higher than that of NC group(252.99±21.13 vs.188.3±21.77,P<0.05).The trend continued until the cage,and the weight of rats in HF group increased significantly during pregnancy.The weight of pregnant rats in the HF group during early,middle and late pregnancy was significantly higher than that in the NC group(335.62±29.03 vs.3297.21±28.72;365.11±26.36 vs.309.2±27.98;412.62±38.66 vs.360.33±35.73 P<0.05).2.Fasting blood glucose in the HF group was significantly higher than that in the NC group during the second trimester of pregnancy(5.43±0.69 vs.4.69±0.73;5.23±0.5 vs.4.78±0.35;5.27±0.51 vs.4.85±0.14,P<0.05).3.The results of OGTT showed that the blood glucose levels of the two groups reached the maximum at 30 min.The blood glucose levels of the HF group at 30 min and 60 min were significantly higher in the NC group(9.57±3.11 vs.6.95±1.25;7.49±1.83 vs.5.24±0.57,P<0.05),the area under the glucose tolerance curve of the HF group was significantly larger than that of the NC group(14.95±0.81 vs.12.48±1.14,P<0.05).4.The levels of insulin and C-peptide in the HF group were significantly higher than those in the NC group(P<0.05).The insulin resistance was significantly increased with the increase of insulin secretion(P<0.05).The HOMA-IR in the HF group was significantly higher in the early,middle and late pregnancy than in the NC group(P<0.05).The HBCI in the HF group was significantly higher in the early pregnancy than in the NC group(P<0.05).The HOMA-IS index was only in the middle.The pregnancy was significantly lower than that of the NC group,which was statistically different(4.88±3.57 vs.11.52±5.47,P<0.05).The rest of the pregnancy was lower than the NC group,but there was no statistical difference.5.In the HF group,the SF was significantly higher than that in the NC group(P<0.05),and the serum ferritin decreased with the increase of gestational age.6.In the HF group,SF was positively correlated with the home,early,middle,and late HOME-IR,and positively correlated with body weight during non-pregnancy,FPG in early pregnancy,FINS in mid-pregnancy,and FPG in late pregnancy(P<0.05).FINS in early pregnancy was negatively correlated(P<0.05),and had no correlation with other indicators.In the NC group,SF was positively correlated with body weight only during non-pregnancy(P<0.05),and was not associated with other indicators.7.The expression of PI3K mRNA in the liver tissue of HF group peaked in the non-pregnancy period,and then decreased with the increase of gestational age,and the lowest in the late pregnancy.The PI3K level in the NC group was higher than that before pregnancy,peaked in early pregnancy and decreased with gestational age.The expression level of IRS1 mRNA in liver tissue of HF group was significantly lower than that of "NC group,and it was not obvious from pre-pregnancy to pregnancy.In the NC group,IRS1 levels decreased during pregnancy,but peaked during late pregnancy.The protein expression of PI3K and IRS1 in liver tissue is basically consistent with mRNA expression.Conclusions:1.In this study,pregnant rats induced by high-fat diet were found to be obese,hyperglycemia,hyperinsulinemia,hyperinsulin resistance and high serum c-peptide,which were consistent with the clinical characteristics of gestational diabetes mellitus,suggesting the success of GDM model establishment.2.Serum ferritin of gestational diabetes rats was significantly higher than that of normal rats during the whole pregnancy,and was positively correlated with insulin resistance.Ferritin levels decreased during pregnancy.It suggested that ferritin was related to the occurrence of GDM.3.The expression of PI3K in the liver of GDM rats was higher than that of normal rats during the whole pregnancy,and significantly decreased during the pregnancy compared with that before the pregnancy,and decreased to the lowest level in the late pregnancy,which was roughly the same as the change trend of serum ferritin.It is hypothesized that PI3K expression in liver is up-regulated under the action of serum ferritin,leading to the occurrence of insulin resistance,and PI3K changes with the fluctuation of serum ferritin.4.The expression of IRS1 in the liver of GDM rats was lower than that of normal rats during the whole pregnancy,and the change was not obvious during the pregnancy,while it was the lowest in the late pregnancy.It is hypothesized that serum ferritin in the liver inhibits the expression of IRS1,leading to the occurrence of insulin resistance,and the involvement is minimized in the third trimester.5.The onset of GDM can be predicted according to the serum ferritin in the early pregnancy,and serum ferritin can be used as the detection index of GDM.Patients with GDM should be carefully supplemented with iron during pregnancy to prevent the high iron status from aggravating the degree of insulin resistance,but the mechanism of SF and IR still needs to be further studied.