Effects Of High-intensity Interval Training On Skeletal Muscle Insulin Resistance In Type 2 Diabetic Mice And Its Mechanism

Object: This article explores high-intensity intermittent training by establishing a mouse model of type 2 diabetes and conducting high-intensity intermittent training for 8 weeks to detect endoplasmic reticulum stress,lipid metabolism and skeletal muscle inflammation-related factors in mouse skeletal muscle.Effects on the insulin resistance of skeletal muscle in type 2 diabetic mice.The possible mechanism for improving highintensity intermittent training to improve insulin resistance in skeletal muscle of type 2 diabetic mice is described as an effective exercise prescription for high-intensity intermittent training.The assistive method of diabetes provides a theoretical basis.Methods:(1)A total of 40 male C57 BL / 6 mice at 4 weeks of age.After one week of standard feeding,30 randomly selected mice were divided into the Con group and the HFD group.The mice in the HFD group continued to be fed a high-fat diet(60% fat,20% protein,20% carbohydrate)for 12 weeks.Later,a single intraperitoneal injection of 1% STZ at a dose of 10 ml / kg induced mice with type 2 diabetes and were randomly divided into a diabetic quiet group(Sed,n = 8)and a diabetic exercise group(HIIT,n = 8);(2)High-intensity intermittent exercise program: run treadmill training on a mouse treadmill at an inclined angle of 15 °,5 days a week(Sunday to Thursday)for 8 weeks;warm up at a speed of 10 m / min before intervention Start 4 minutes,then perform 10 high-intensity runs of 4 minutes,interspersed with 2 minutes of active rest(gradual deceleration to 0m / min),and the running speed gradually increased from 10 m / min to 26 m / min within 8 weeks;(3)After the successful modeling,the mice were subjected to a fasting blood glucose test,a glucose tolerance test,and an insulin tolerance test before and after the exercise intervention;(4)After 8 weeks of exercise,the gastrocnemius muscles of the mice were taken,and oil red o staining was used to examine the fat deposition of skeletal muscle.RT-PCR was used to detect fatty acid oxidation,endoplasmic reticulum stress,macrophage markers,and m RNA expression levels of inflammation-related factors.Result:(1)Establishment of STZ-induced diabetes model After 12 weeks of high-fat feeding,the body weight of HFD mice was 1.5 times that of the Con group.After intraperitoneal injection of STZ,the fasting blood glucose of mice in the HFD group was significantly higher than that in the Con group(p <0.01).The area under the curve was significantly higher than that in the Con group(p <0.01),and the expressions of insulin resistance-related genes PI3 K,AKT,IRS-1,and GLUT4 were significantly reduced(p <0.01).The type 2 diabetes model was successfully constructed.(2)Effect of high-intensity intermittent exercise on type 2 diabetic mice Compared with the mice in the Sed group,after 8 weeks of high-intensity intermittent training,the weight of the mice in the HIIT group was significantly reduced(p <0.01).The area under the curve after glucose and insulin decreased significantly(p <0.01);genes related to insulin signaling pathway PI3K(p <0.01),AKT(p <0.01),IRS-1(p <0.05)and GLUT4(p <0.01)m RNA expression increased significantly.(3)The effect of high-intensity interval training on the skeletal muscle of type 2 diabetic mice(1)Effect of high-intensity intermittent exercise on skeletal muscle endoplasmic reticulum stress in type 2 diabetic mice Compared with the Con group,the m RNA expression levels of UPR-related genes GRP78(p <0.01),PERK(p <0.01),IRE-1?(p <0.01),and ATF-6(p <0.05)in the skeletal muscle of the Sed group of mice Significantly increased,m RNA expression levels of endoplasmic reticulum stress-related genes CHOP(p <0.05),ATF-4(p <0.01),and TRB3(p <0.05)significantly increased,and endoplasmic reticulum stress downstream-acting genes JNK(p <0.05),NF-?B(p <0.01),IKK?(p <0.05)also increased significantly;after 8 weeks of high-intensity intermittent training,compared with the Sed group,the skeletal muscle UPR-related protein GPR78 in the HIIT group,PERK,IRE-1?,ATF6 m RNA expression levels were significantly reduced(p <0.01),endoplasmic reticulum stress-related genes CHOP,ATF4,TRB3 m RNA expression levels were significantly reduced(p <0.01),its downstream related genes JNK,The expressions of NF-?B and IKK? also decreased significantly(p <0.01).(2)Effects of high-intensity intermittent exercise on skeletal muscle lipid metabolism in type 2 diabetic mice Oil red o staining showed that there was lipid deposition in the skeletal muscle and skeletal muscle cells of the Sed group.After eight weeks of high-intensity intermittent training,compared with the Sed group,fatty acid oxidation-related factors AMPK in the HIIT group(P <0.01),PPAR-?(p <0.01),PGC-1?(p <0.05)m RNA expression levels increased significantly,and skeletal muscle fat deposition was improved.(3)Effect of high-intensity intermittent exercise on skeletal muscle inflammation in type 2 diabetic mice Compared with the Con group,the m RNA expression of total macrophage marker F4 / 80 in the skeletal muscle of the Sed group increased significantly(p <0.05),and the M1 type macrophage markers i NOS(p <0.05),CD86(The expression of p <0.01)increased significantly,while the expression of M2 macrophage marker ARG1(p <0.01) decreased significantly.Although the expression of CD206 also decreased,it did not reach a significant difference.The m RNA expression of anti-inflammatory factor IL-13 The levels were significantly reduced(p <0.05),and the expression level of IL-10 also decreased,but did not reach statistical differences.The proinflammatory factors IL-6(p <0.01),TNF-?(p <0.05),TGF-?(P <0.05)and IL-1?(p <0.01)increased significantly.After 8 weeks of high-intensity intermittent training,skeletal muscle macrophages were transformed from M1 to M2,which improved the occurrence and development of skeletal muscle inflammation.Compared with Sed group mice,total macrophage markers in HIIT group mice The expression of F4 / 80 was significantly reduced(p <0.01),the expression of M1 macrophage markers i NOS and CD86 was significantly reduced(p <0.01),and the expression of M2 macrophage markers ARG1 and CD206 was significantly increased(p <0.01).<0.01),m RNA expression levels of anti-inflammatory factors IL-13 and IL-10 increased significantly(p <0.01),and expression levels of proinflammatory factors IL-6,TNF-?,TGF-?IL-1? significantly decreased(p <0.01).Conclusion(1)Compared with the control group,the weight and fasting blood glucose of diabetic mice were significantly increased,glucose and insulin tolerance were significantly reduced,and the expression of genes related to islet signaling pathway was suppressed;(2)Compared with the diabetic quiet group,8 weeks of high-intensity interval training can significantly reduce the weight of diabetic mice,improve systemic insulin sensitivity and improve insulin resistance.At the same time,exercise can improve skeletal muscle insulin resistance,its mechanism may be related to skeletal muscle fat deposition,inflammation and endoplasmic reticulum stress improvement.