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The Expression and Significance of IRS-1and Gsk-3in High Fat and Sugar Diet Fed Pregnancy Rat

Author: XuZuoZuo
Tutor: ZhangSuHe
School: Zhengzhou University
Course: Internal Medicine
Keywords: Pregnant rats with abnormal glucose metabolism gestational diabetesmellitus IRS-1 GSK-3
CLC: R587.1
Type: Master's thesis
Year: 2012
Downloads: 85
Quote: 0
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BackgroundGestational diabetes mellitus (Gestational diabetes mellitus, GDM) was serious harmful to maternal and child as an independent special type, after delivery the risk of type2diabetes significantly increased, the present study indicated that the insulin resistance (insulin resistance, IR)、environmental factors and unreasonable high-fat diet played more and more important roles in the main pathogenesis mechanism. Insulin receptor substrate-1(insulin receptorsubst rate-1, IRS-1) is the insulin receptor substrate which was the earliest discovered and predominantly express in skeletal muscle tissue, it was an important regulator in insulin signal transduction pathways.The defects of expression functional of IRS-1taked part in insulin resistance.Glycogen synthase kinase (glycogen synthase kinase-3, GSK-3) was a key enzyme in the pathway of glycogen synthesis, through phosphorylation of glycogen synthase it inactivated glycogen synthesis, it induced hyperglycemia. In the skeletal muscle tissue the overexpression of GSK-3and excessive activation had a certain relationship with the insulin resistance. But the relationship of these two factors with abnormal glucose metabolism during pregnancy was unclear, and the molecular mechanism of dietary intervention which improved insulin resistance needed further research ObjectivesThis study set up the pregnancy rat model with sugar metabolic abnormalities,and observed a preliminary expression of IRS-1and GSK-3in the skeletal muscle tissue.Subjects and MethodsForty female SD rats were divided into five groups:pregnant rats fed with sucrose and fat diet (SFP), pregnant rats fed with normal diet (NP), virgin rats fed with sucrose and fat diet (SFV), virgin rats fed with normal diet (NV), diet intervention for pregnant rat (GHP)group.In the three groups we matched two female rats with one male rat.On the twentieth day of gestation,we took the blood of the hearts to test the blood glucose and the insulin used to calculate insulin resistance index,the RT-PCR was used to detected the expression of IRS-land GSK-3. With the SPSS for Windows17.0statistical analyse software,we analysised and comparised data of the insulin, total cholesterol, triglyceride, insulin resistance index, expression level of muscle tissues’IRS-1and GSK-3mRNA between five groups.Results1. The result of the data of the TG,IR index and FINS:in the SPF group,it was higher than that of other three groups, and it had a statistically significant difference (p<0.05); when the GHP group compared with SFP group, it obviously decreased (p <0.05);when the GHP group compared with NP group, it obviously increase (p <0.05)2.The result of OGTT:in SFP group, it hinted the blood sugar levels of0min,30min,60min,120min increased, which had a statistically significant difference (p<0.05);the data of the NP group and SFV group’s compare with the NV group’s,it obviously decreased (p<0.05);when the GHP group compared with SFP group, it decreased (p<0.05);when the GHP group compared with the NP group, it increase (p<0.05)3. The result of the IRS-1mRNA’s RT-PCR showed that the expression of IRS-1in SFP group was significantly lower than that of other three groups (p<0.05);the SFP group and NP group were both lower than that of NV group (p<0.05); when the GHP group compared with the SFP group, it was higher (p<0.05);when the GHP group compared with the NP group, it was lower(p<0.05).4. The result of the GSK-3mRNA’s RT-PCR showed that the expression of GSK-3in SFP group was significantly higher than that of other three groups (p<0.05);the SFP group and NP group were both higher than that of NV group’s (p<0.05); when the GHP group compared with the SFP group,it decreased(p<0.05); when the GHP group compared with NP group, it increased (p<0.05)5. Correlation analysis revealed:in the skeletal muscle tissue of the SFP group’s, the expression of GSK-3was negatively correlated with the insulin resistance (r=0.690,p=0.012); the expression of IRS-1was positively correlated with the insulin resistance (r=-0.785,p=0.023); the expression of GSK-3was negatively correlated with the expression of IRS-1(r=-0.815,p=0.039)Conclusions1. Compared with the disease of abnormal glucose metabolism during pregnancy, the pregnant rats fed with the sucrose and fat diet has the similar pathologic changes,this suggests that it could be researched as a model of GDM.2.When the rats is fed with the high sugar and fat diet,the expression of the IRS-1mRNA is lower and the expression of GSK-3mRNA is higher, it reveals that the two factors might both take part in the insulin resistance.3. In the dietary intervention group,the expression of the IRS-1mRNA and GSK-3mRNA’s change, it reveals that these two factors can improve the insulin resistance.

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