Study Of Insulin Receptor Substrate In Obese And Type 2 Diabetes Children

Objective: To study changes of insulin function indicators and explore the relation of insulin receptor substrate(IRS) and obese and type 2 diabetes children . Methods: we use immunocytochemistry techniques staining white blood cell and use image analysis software to measure staining response, produce optical density values, thus more quantitative analysis insulin receptor substrate-1,2 content changes in white blood cell, and measure fasting plasma glucose , fasting plasma insulin , fasting plasma C peptide were performed in 20 obese and 20 type 2 diabetes children and 20 control children.Homeostasis model assessment β cell (HOMA-P), Homeostasis model assessment-insulin resistance (HOMA-IR), homeostasis model assessment-insulin activity index (LAI), body mass index (BMI) are calculated. Results: There are no significant differences in fasting plasma glucose levels (P>6.05), fasting plasma C peptide levels(P>0.05), HOMA-p(P>0.05), HOMA-IR(P>0.05), in obese children and control children, while significant differences existed in fasting plasma glucose levels(P<0.05) ,IAI(P<0.05), IRS-1 content(P<0.05), BMI(P<0.05) in obese children and control children.There are significant differences in and fasting plasma glucose levels(P<0.05), fasting plasma insulin levels(P<0.05), HOMA-P(P<0.05),HOMA-IR (P<0.05), IAI(P<0.05), IRS-l(P<0.05), BMI(P<0.05) in type 2 diabetes children and control children, while no significant differences in fasting plasma C peptide levels(P>0.05),IRS-2 content (P>0.05).In 3 group BMI content have no significantly correlated with FPG (P>0.05),FDSfS(P>0.05), C peptide(P>0.05),HOMA -p(P>0.05),HOMA-IR(P>0.05), IAI(P>0.05), IRS-l(P>0.05), IRS-2(P>0.05). In 3 group IRS-1 content have no significantly correlated with FPG(P>0.05), FINS (P>0.05), HOMA-P(P>0.05), HOMA-IR(P>0.05), IAI(P>0.05), IRS-2(P>0.05) and IRS-2 content have no significantly correlated with FPG(P>0.05), C peptide(P>0.05),HOMA-IR(P>0.05). In obese and type 2 diabetes children IRS-2 content have no significantly correlated with FINS(P>0.05), HOMA-p(P>0.05),IAI(P>0.05). In control children IRS-2 content have negatively significantly correlated with FINS, HOMA-IR,(respectively r=-0.497 P<0.05;r=-0.728 P<0.05) and have positively significantly correlated with IAI (r=0.447 P<0.05) . Conclusion:1.There are no significant differences in fasting plasma glucose levels (P>0.05), fasting plasma C peptide levels(P>0.05), IRS-2 content (P>0.05), HOMA-p(P>0.05),HOMA-IR(P>0.05) in obese children and control children, while significant differences exist in fasting plasma glucose levels (P<0.05),IAI(P<0.05), IRS-1 content(P<0.05), BMI(P<0.05) in obese children and control children.It's confirmed the idea that in obese children blood beta cell function is to maintain normal plasma glucose levels, but show insulin resistance. The obese group and the control group do not show differences ,but obese children's beta cells are in a practical "excessive state".This "excessive" will result in a blood beta cell function missing payment and eventually type 2 diabetes can be addressed to occur.2.There are significant differences in fasting plasma glucose levels(P<0.05), fasting plasma insulin levels (P<0.05), HOMA-P(P<0.05),HOMA-IR(P<0.05), IAI(P<0.05), BMI(P<0.05) in type 2 diabetes children and control children, while no significant differences in fasting plasma C peptide levels(P>0.05). The patientshave insulin sensitivity reducing, fasting plasma glucose rising, insulin secretion significantly increasing.This suggest type 2 diabetes patients have hyperinsulinemia and significant insulin resistance.3. In 3 group BMI content have no significantly correlated with FPG, FINS, C peptide, HOMA-p\HOMA-IR, IAI, IRS-1, IRS-2 (P>0.05). This suggest regardless of how BMI is, obese and type 2 diabetes children have the same risks suffering insulin resistance and beta cells' function damage .4. There are significant differences in IRS-1 in obese.type 2 diabetes children and control children(P<0.05). There were no significant differences in IRS-2 in obese, type 2 diabetes children and control children (P>0.05). This show the patients have the key insulin receptor substrate lossing in insulin receptors signal transmission and affect insulin role to play. In normal circumstances, in insulin signal transmission IRS-1 play a leading role, IRS-2 role may not evident. But when IRS-1 is constrained, IRS-2 become a major substrate compensatory increasing, but it needs a higher concentration of insulin to combine p85 in the transmission signal, which may be a key reason of insulin resistance in obese and type 2 diabetes children.5.1n 3 group IRS-1 content have no significantly correlated with FPG (P>0.05), FINS (P>0.05), C peptide(P>0.05),HOMA -p(P>0.05),HOMA-IR(P>0.05), IAI(PX).O5), IRS-2(P>0.05), and IRS-2 content have no significantly correlated with FPG(P>0.05), C peptide (P>0.05),HOMA-IR(P>0.05). In obese and type 2 diabetes children IRS-2 content have no significantly correlated with FINS(P>0.05), HOMA-p(P>0.05),IAI(P>0.05). In control children IRS-2 content have negatively significantly correlated with FINS, HOMA-IR (r=-0.497 P<0.05;r=-0.728 PO.05), have positively significantly correlated with IAI (r=0.447 P<0.05). This indicate whether insulin function impair, IRS-1, IRS-2 have changes and the degreehave no significantly correlated with the degree of insulin functional damage.In the control children IRS-2 have correlated with insulin concentration, insulin concentration higher, IRS-2 content lower and HOMA-IR lower, insulin sensitivity higher, IRS-2 content higher.6.This suggest IRS-1 and IRS-2 have affects in insulin resistance and have benefit to further understand pathogenesis of type 2 diabetes, guide clinical treats.