Endurance Of Treadmill Training On Gk Rat Liver Cells Endoplasmic Reticulum Stress And The Effects Of Insulin Resistance And Its Molecular Mechanism Research

Diabetes has become one of the main threat to human health disease of the 21st century, which is mainly type 2 diabetes.The core characteristic of type 2 diabetes is insulin resistance.Recently more and more studies have shown that endoplasmic reticulum stress can induce unfolded protein response to affect insulin signaling pathways, leading to insulin resistance.Endoplasmic reticulum stress of several major landmark molecules, they express the changes to the extent of the endoplasmic reticulum stress reaction, such as immunoglobulin heavy chain-binding protein, protein kinase R like endoplasmic reticulum kinase, etc.What,s more,many literature shows that long-term movement can reduce endoplasmic reticulum stress and lots of literature also shows that long-term endurance exercise also has certain effect of prevention and treatment on type 2 diabetes.It’s not hard to think that whether endurance exercise through UPR induced by endoplasmic reticulum stress ways affects insulin signaling pathway.Therefore, the article explores the mechanism of type 2 diabetes mainly through long-term endurance exercise on the relationship between the endoplasmic reticulum stress and insulin resistance influence for the prevention and treatment of type 2 diabetes to provide theoretical basis and data support.Objective:The article regards GK rat as model of type 2 diabetes and endurance of the six weeks run training intervention with these rat.Then we check liver IRE1/JNK/IRS1 pathways to observe relationship between UPR signaling pathway caused by endoplasmic reticulum stress and insulin signaling pathway in order to provide theoretical basis for the treatment of type 2 diabetes.Methods:16 GK rats were randomly divided into diabetic group (D) and diabetes movement (DE);16 Control male Wistar rats were randomly divided into control group (C) and exercise groups (E). Group E and DE run for 6 weeks endurance exercise with the increasing speed weekly respectively,16,17,18,19,2015 m/min, duration of 1h, exercise 6 days a week, Sunday rest.QPCR detects liver BiP, IRE1, JNK1, JNK2 and IRS1 relative mRNA expression of AKT2;Western Blotting tests BiP, JNK1, JNK2 and P-JNK,AKT protein expression.Results:(1) Compared with group C, group E weight of rats decreased significantly (P< 0.05). As is compared with group D, DE group rats weight decreased significantly (P< 0.05).Compared with group C, group D weight of rats decreased significantly (P< 0.01). Compared with group E, DE weight of rats decreased significantly (P< 0.01).(2) Compared with group C,there is no obvious change in group E in fasting plasma glucose in rats. As is compared with group D, there is no obvious change in DE group in fasting plasma glucose in rats.Compared with group C, group D rats significantly elevated fasting glucose (P< 0.05).Compared with group E, DE rats significantly elevated fasting glucose (P< 0.01).(3) Compared with group C, group E of the BiP mRNA expression and BiP protein expression had no significant difference;Similarly, group D BiP mRNA expression has a rising trend, while the BiP protein expression there was no significant difference.Compared with group E, DE group of BiP mRNA expression and BiP protein expression had no significant difference.Compared with group D, DE group of BiP mRNA expression and BiP protein expression also had no significant difference.(4)IRE1 and IRS1 had no significant difference between groups.(5)Compared with group C,there was no significant difference in group E in JNK1, JNK2 mRNA expression,the rise of JNK1 protein expression had significant difference (P< 0.05) and JNK2 protein expression had no significant difference.Compared with group C, there was no significant difference in group D JNK1 and the expression of JNK2mRNA. The rise of JNK1 protein expression had significant difference (P< 0.05) and JNK2 express a downward trend.Compared with group D, there was no significant difference in DE JNK1, JNK2mRNA, JNK1, JNK2 protein expression.Compared with group E, DE group of JNK1 mRNA and JNK2 protein expression significantly reduced (P< 0.05),JNK2mRNA expression is on the rise and there is no significant difference in JNK1 protein expression.From the overall JNK and P-JNK protein expression level,there is no significant differences every group.From the point of JNK activity, compared with group C, group E JNK activity is on the decline, group D JNK activity is on the rise.Compared with group E, DE group JNK activity is on the rise.Compared with group D, DE group JNK activity is downward trend.(6)Compared with group C, there was no significant difference in group E of AKT2 mRNA expression and AKT protein expression and there were no significant difference in group D AKT2 mRNA expression and group D AKT protein expression was significantly decreased (P< 0.01).Group compared with group D, there was no significant difference in DE AKT2 mRNA expression and AKT protein expression.Compared with group E, there were no significant difference in DE group of AKT2 mRNA expression, DE group AKT protein expression was significantly decreased (P< 0.01). Conclusion:(1)Diabetic rats significantly reduce weight and long-term endurance training can significantly reduce the normal rats and diabetic rats weight.Diabetic rats significantly elevated fasting glucose and six weeks of endurance training did not have a significant impact on fasting glucose in rats.(2)Diabetic rats liver BiP mRNA level tends to rise, but the BiP protein and endoplasmic reticulum stress molecules had no significant difference between groups in terms of the expression of IRE1, which indicates there is no relationship between the happening of endoplasmic reticulum stress and insulin resistance.(3)Diabetic rats liver IRE1mRNA levels did not change but its downstream JNK1 protein expression level increased significantly, the level of JNK2 has no obvious difference, which indicate that endoplasmic reticulum stress influences insulin signaling pathway mainly through the influence of JNK1 expression. Six weeks of treadmill endurance training showed a decreased diabetic rats liver JNK1 expression of transcription and translation level trend, while there is no change in IRS 1 mRNA express between groups, which suggests that insulin receptor upstream did not change and is not the main cause of the insulin resistance.Downstream of the diabetic rats liver AKT protein expression suppression present state of insulin resistance,which suggests that insulin signaling pathway is inhibited.Movement can reduce the JNK1 expression and insulin resistance.