耐力训练时脂肪甘油三酯脂肪酶与工作肌糖代谢和线粒体密度——基于ATGL基因敲除小鼠的研究

目的:(1)观察ATGL基因敲除小鼠耐力训练时胰岛素抵抗、工作肌糖转运蛋白及线粒体密度的变化;(2)测定Akt、PKC、PPAR-α蛋白激活及含量,探究其与胰岛素抵抗、工作肌糖转运蛋白及线粒体密度的变化之间的关系。方法:ATGL-/-、ATGL+/-和C57BL/6J小鼠跑台耐力训练训练7天,测定小鼠体重、肌糖原、血糖、血胰岛素和胰岛素抵抗,蛋白印记法测定腓肠肌和比目鱼肌GLUT-4(内外膜)、p-Akt、Akt、p-PKC、PKC含量和PPAR-α水平。结果:(1)运动训练后,腓肠肌和比目鱼肌糖原含量、HOMA-IR指数存在基因类型、运动训练的差异(P<0.05)。运动训练引起血糖和血胰岛素在基因类型的差异(P<0.05)。(2)运动训练后,腓肠肌和比目鱼肌Akt、PKC、磷酸化水平、腓肠肌总Akt、PPAR-α蛋白表达存在基因类型、运动训练的差异(P<0.05)。比目鱼肌总Akt表达、腓肠肌和比目鱼肌总PKC、PPAR-α蛋白运动训练的差异不具有显著性意义(P>0.05)。结论:耐力训练时,ATGL通过上调Akt和PKC促进胰岛素敏感性和改善胰岛素抵抗;ATGL上调PPAR-α起到促进线粒体含量。

Effect of berberine on glucolipid metabolization in diabetic skeletal muscle and its mechanism

Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.

Glycogen storage diseases: New perspectives

Glycogen storage diseases （GSD） are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type I a involves the liver, kidney and intestine （and I b also leukocytes）, and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type Ilia involves both the liver and muscle, and lib solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type Ⅵ and Ⅳ are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type Ⅺ is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type Ⅱ is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and Ⅶ involve only the muscle.

A correlation study of the expression of resistin and glycometabolism in muscle tissue after traumatic brain injury in rats

Objective： To investigate the expression pattern of resistin （RSTN） in skeletal muscle tissue and its influence on glycometabolism in rats with traumatic brain injury （TBI）. Methods： Seventy-eight SD rats were randomly divided into traumatic group （n=36）, RSTN group （n=36） and sham operation group （n=6）. Fluid percussion TBI model was developed in traumatic and RSTN groups and the latter received additional 1 mg RSTN antibody treatment for each rat. At respectively 12 h, 24 h, 72 h, 1 w, 2 w, and 4 w after operation, venous blood was collected and the right hind leg skeletal muscle tissue was sampled. We used real-time PCR to determine mRNA expression of RSTN in skeletal muscles, western blot to determine RSTN protein expression and ELISA to assess serum insulin as well as fasting blood glucose （FBG） levels. Calculation of the quantitative insulin sensitivity check index （Q value） was also conducted. The above mentioned indicators and their correction were statistically analyzed. Results： Compared with sham operation group, the RSTN expression in the skeletal muscle as well as serum insulin and FBG levels revealed significant elevation （P〈0.05）, and reduced Q value （P〈0.05） in traumatic group. Single factor linear correlation analysis showed a significant negative correlation between RSTN expression and Q values （P〈0.001） in traumatic group. Conclusion： The expression of RSTN has been greatly increased in the muscular tissue of TBI rats and it was closely related to the index of glycometabolism. RSTN may play an important role in the process of insulin resistance after TBI.

Regulation of autophagy by tea polyphenols in diabetic cardiomyopathy

Objective： To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyo- pathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. Methods： Sixty Sprague-Dawley （SD） rats were randomly divided into six groups： a normal control group （NC）, an obesity group （OB）, a diabetic cardiomyopathy group （DCM）, a tea polyphenol group （TP）, an obesity tea polyphenol treatment group （OB-TP）, and a diabetic cardiomyopathy tea polyphenol treatment group （DCM-TP）. After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ul- trasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-11, SQSTM1/p62, and Beclin-1 were determined by Western blotting. Results： Com- pared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-11/I and Beclin-1 increased obviously whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups （P〈0.05）. Conclusions： Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.