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The Effect Of Treadmill Training On Mitochondrial Unfolded Protein Response And Insulin Resistance In The Skeletal Muscle Of GK Rats As Well As Its Underlying Mechanism

Posted on:2017-03-12Degree:MasterType:Thesis
Country:ChinaCandidate:H X JinFull Text:PDF
GTID:2297330485463428Subject:Human Movement Science
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Background:With the development of economy and the improvement of people’s living standard, tremendous changes have taken place in lifestyle and diet of people. The incidence of obesity has increased rapidly due to eating a high-fat and high-sugar diet which results in the increasingly high population of Type Ⅱ Diabetes Mellitus. If diabetic patients are not treated timely and effectively, it will bring heavy financial burden to social and family caused by diabetes complications. So it is necessary to find effectively treatment methods and new thoughts of pathomechanism on Type Ⅱ Diabetes Mellitus.In recent years, many experiments have demonstrated that it will trigger body’s adaptive defense ways and prolong life-span when the body is given moderate intensity of stress. As a way of stress, different types of exercises contribute to stress response in mitochondria which could reveal pathomechanism of several diseases with new thoughts.When a certain intensity of stress appears, unfolded and misfolded proteins will accumulate in mitochondira, activating some signal molecules and maintaining protein homostasis as a result of mitochondrial homeostasis which is a process called unfolded protein response in mitochondria. In recent years, experiments show that there is a close relationship between the occurrence of diseases and unfolded protein response in mitochondria. Although the majority of researches are focusing on the unfolded protein response mechanism in neurodegenerative diseases, there is a potential relationship between Type Ⅱ Diabetes Mellitus and unfolded protein response in mitochondria which has gradually been in a hot research. On the basis of exploring the relationship between Type Ⅱ Diabetes Mellitus and unfolded protein response in mitochondria, the GK rats (Type Ⅱ Diabetes Mellitus model) are imposed on treadmill endurance activity to investigate the effect of exercise on unfolded protein response in mitochondria.Objectives:After imposing 6 weeks of treadmill endurance activity on rats, the expression of several moleculars have been detected in this paper, such as ERa, CHOP, C/EBPβ of unfolded protein response in mitochondria, Parkin, PINK1 in mitophagy and BiP, JNK2 of unfolded protein response in-endoplasmic reticulum to explore the effect of exercise on unfolded protein response in mitochondria of GK rats.Methods:Clean grade male rats of 12 weeks old including16 GK (Goto Kakiski Wistar) rats and 16 Wistar rats were used in this paper. GK rats were divided into 2 groups including D group and DE group. Wistar rats were also divided into 2 groups including C group and E group. All of them were raised in standard environment. Both of rats of DE and E groups were running in the treadmill for 6 weeks and speeds were 15,16,17,18,19,20 m/min respectively, time of duration was 1 hour per day and running for 6 days per week except for Sunday. Before killing them, rats were weighed every certain days and were tested sugar levels on 06/11 and 22/12. The relative mRNA expression of BiP, JNK2, CHOP, HSP60, Lonp, PINK1, Parkin were detected in this paper. Meanwhile, the relative protein expression of ERα, C/EBPβ, CHOP, PINK1, Parkin were detected in this paper.Results:(1) Generally, both on 06/11 and on 22/12, Rats’blood glucose level in D group and DE group in fasting,15min after eating,30min after eating,60min after eating,90min after eating, 120min after eating were significantly higher than C group and E group (P<0.05), besides, rats in D group had the highest blood glucose which followed by DE group.(2) The mRNA expression of key factors were measurred in unfolded protein response in mitochondria, mitophagy, unfolded protein response in endoplasmic reticulum, such as HSP60, Lonp, BiP, JNK2, CHOP, PINK1, Parkin. Data revealed that:1) There was no significant difference among those 4 groups in terms of HSP60 and LonP.2) Compared with C group, the relative mRNA expression of BiP, JNK2 and Parkin in rats in E group significantly declined (P<0.05) and (P<0.01); Compared with D group, there was a significante increase regarding the expression of CHOP (P<0.05),and there was a more significante decrease in terms of the expression of BiP and JNK2 in DE group(P<0.01).3) Compared with E group, there was a significante increase regarding the expression of PINK1 in DE group (P<0.01).(4) In this paper, the protein expression of key factors were measured in unfolded protein response in mitochondria and mitophagy, such as ERα, C/EBPβ, CHOP, PINK, Parkin. Datas reveal that:1) Compared with C group, there was a significante decrease in terms of the expression of ERa in E group (P<0.05).2) There was no significant difference among those 4 groups in terms of C/EBPβ.3) Compared with D group, there was a significante increase regarding the expression of CHOP, PINK1 and Parkin in DE group (P<0.05).Conclusions:(1) Datas reveal that the 6-week treadmill endurance activity is a stress that leads to cell death though apoptosis under condition of Type Ⅱ Diabetes Mellitus, however in the physical condition, this type of activity promotes cell to survive via activating unfolded protein response in mitochondria.(2) Datas reveal that the 6-week treadmill endurance activates mitophagy under condition of Type Ⅱ Diabetes Mellitus, however in the physical condition, this type of activity inhibits mitophagy.(3) Datas reveal that the 6-week treadmill endurance activates unfolded protein response in endoplasmic reticulum under condition of Type Ⅱ Diabetes Mellitus, however in the physical condition, this type of activity inhibits unfolded protein response in endoplasmic reticulum.
Keywords/Search Tags:Exercise, Type Ⅱ Diabetes Mellitus, Unfolded protein response in mitochondria, Mitophagy, Unfolded protein response in endoplasmic reticulum
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