运动促进甘丙肽分泌对大鼠骨骼肌细胞胰岛素敏感性的影响

目的探查运动导致的甘丙肽(GAL)分泌增加,能否提高大鼠骨骼肌细胞胰岛素敏感性。方法大鼠分4组:安静对照组及运动对照组均注射生理盐水,安静用药组及运动用药组注射GAL受体拮抗剂M35。两运动组鼠游泳60 min/d,计14 d。用正糖钳了解胰岛素敏感性,测血清GAL和骨骼肌细胞葡萄糖转运蛋白(GLUT)4浓度及GLUT4 mRNA表达水平。结果两用药组GLUT4 mRNA表达水平、骨骼肌细胞内外膜GLUT4含量和正糖钳实验的葡萄糖输注速率比相应对照组均有显著下降,骨骼肌细胞外膜与细胞总膜GLUT4含量比也下降。而两运动组上述指标及GAL浓度比相应安静组均有显著增加。结论运动诱导GAL浓度增高,可通过增加骨骼肌细胞GLUT4浓度和促进GLUT4向细胞外膜转运而提高胰岛素敏感性。     

蛋白激酶B与葡萄糖转运调节

在糖耐量异常，2型糖尿病患者及鼠模型的骨骼肌和脂肪组织中蛋白激酶B（PKB）的含量下降，其在胰岛素刺激下向细胞膜的转移量也明显降低。利用PKB抑制剂ML9或无酶活性及磷酸化缺陷的AAA-Akt，可完全阻止鼠脂肪细胞或L6成肌细胞葡萄糖转运和葡萄糖转运子4（GLUT4）易位，此外，氧化，渗透应激可抑制胰岛素刺激的PKB激活作用。该作用与胰岛素刺激的葡萄糖转运活性受损类似。     

GLUT4与胰岛素抵抗

大量研究证实，葡萄糖转运蛋白4（GLUT4）的表达或活性下降导致的骨骼肌和脂肪细胞对葡萄糖摄取、利用的减少是胰岛素抵抗的重要分子基础。对GLUT4分子表达的研究有助于进一步阐明胰岛素抵抗的发生机制和发现防治胰岛素抵抗的新方法。     

GLUT4 mRNA在糖尿病大鼠骨骼肌及脂肪组织中的表达及意义

目的探讨葡萄糖转运蛋白4（GLUT4）mRNA表达在2型糖尿病发病中的作用。方法将46只SD大鼠随机分为对照组及高脂组各10只、高血糖组及糖尿病组各13只,分别采用高脂饮食及腹腔内注射链脲佐菌素方法制备高脂、高血糖及2型糖尿病模型。10周末实验结束后,分别取血测空腹血糖（FBG）、空腹胰岛素（FINS）,计算胰岛素指数（ISI）;采用RT-PCR检测骨骼肌、脂肪组织中GLUT4 mRNA表达。结果与对照组比较,糖尿病组FBG、FINS及ISI显著升高、骨骼肌及脂肪组织中GLUT4 mRNA表达均明显下调,高血糖组、高脂组骨骼肌和脂肪组织中GLUT4 mRNA表达亦显著低于对照组,四组GLUT4 mRNA在骨骼肌中的表达均显著高于脂肪组织（P〈0.01、0.05）。结论 GLUT4 mRNA在骨骼肌中的表达高于脂肪组织;高脂饮食、高血糖可通过下调GLUT4 mRNA表达加重胰岛素抵抗,进而诱发2型糖尿病。     

增龄对大鼠骨骼肌细胞葡萄糖转运蛋白的影响

目的　探讨增龄对大鼠骨骼肌细胞葡萄糖转运蛋白4(glucose transporter 4,GLUT4)的影响。　方法　SD实验大鼠分为2组青年组（3月龄）和老年组（24月龄）各式各样0只。制务GLUT4羧基端正2肽的多克隆抗体,利用Western印迹法检测2组大鼠骨骼肌细胞GLUT4蛋白含量,并检测大鼠尾静脉血糖。　结果　老年组大鼠的血糖（5.6±0.5mmol/L)略高于青年组大鼠（4.5±0.5mmol/L),但差异无显著性;青年组大鼠骨骼肌细胞内GLUT4相对含量为109.62±12.25,而老年组为86.46±8.25,差异有显著性（P<0.05)。　结论　增龄可引起大鼠骨骼肌细胞GLUT4蛋白含量明显减少,使骨骼肌细胞对葡萄糖的转运发生障碍,这可能是老年人易产生胰岛素抵抗的机制之一。     

运动对胰岛素刺激的老年雌性鼠骨骼肌细胞葡萄糖转运因子4转位的影响

我们应用老年小鼠模型制备完整的骨骼肌束，研究运动对胰岛素刺激的骨骼肌细胞葡萄糖转运因子4（Glucose transporter 4，GLUT4）转位的影响，探讨运动改善骨骼肌细胞对胰岛素敏感性和减少骨骼肌细胞胰岛素抵抗（IR）的机制。     

运动后甘丙肽分泌对大鼠胰岛素敏感性的影响

目的 探讨运动后甘丙肽(Galanin,Gal) 分泌对大鼠胰岛素敏感性的影响.方法 大鼠分4组:安静对照组及运动对照组均注射生理盐水,安静用药组及运动用药组注射Gal受体拮抗剂Galantide.两运动组鼠正式游泳10 d,60 min/d.用正糖钳了解胰岛素敏感性,检测空腹胰岛素、血糖及骨骼肌细胞膜葡萄糖转运蛋白4(GLUT4)含量.结果 运动对照及运动用药组正糖钳的葡萄糖输注速率比相应安静组分别有极显著(P＜0.01)及显著增加(P＜0.05),两用药组比相应对照组有极显著下降(P＜0.01);两用药组实验后比实验前胰岛素均显著增加(P＜0.05),安静用药组实验后比实验前以及与安静对照组实验后相比血糖明显增加(P＜0.05);运动对照及运动用药组比相应安静组骨骼肌细胞膜GLUT4分别提高26%(P＜0.01)及17.8%(P＜0.05).结论 运动诱导Gal浓度增高,可通过增加GLUT4浓度和促进GLUT4向细胞膜转运提高胰岛素敏感性.     

黄芪多糖降糖作用及其对蛋白激酶B和葡萄糖转运蛋白4的影响

运用黄芪多糖治疗2型糖尿病大鼠,检测其血糖、血胰岛素水平、蛋白激酶B(PKB/Akt)活性和葡萄糖转运蛋白4转位的变化.结果 显示,黄芪多糖有降糖作用,其机制可能与增强糖尿病大鼠骨骼肌组织对胰岛素的敏感性、提高PKB/Akt活性和葡萄糖转运蛋白4转位有关.     

罗格列酮上调高脂饮食老年大鼠骨骼肌GLUT4和PKB的表达

目的 观察高脂饮食对老年大鼠骨骼肌葡萄糖转运蛋白4(GLUT4)和蛋白激酶B(PKB)的表达变化及罗格列酮的干预效果.方法 老年大鼠随机分为对照组、高脂组(HF)、高脂+罗格列酮干预组(RSG),每组20只.应用清醒状态下正常葡萄糖高胰岛素钳夹技术的葡萄糖输注率评价胰岛素抵抗,用荧光定量PCR法和Western印迹技术检测骨骼肌GLUT4和PKB的表达.结果 高脂组骨骼肌长链脂酰辅酶A(LCACoA)升高而葡萄糖输注率明显下降(P＜0.01),骨骼肌GLUT4和PKB的表达明显降低(P＜0.05,P＜0.01),罗格列酮干预组显著缓解高脂组上述变化(P＜0.05,P＜0.01).结论 罗格列酮上调高脂饮食老年大鼠骨骼肌GLUT4和PKB的表达,是改善老年胰岛素抵抗的机制之一.     

蛋白激酶B与葡萄糖转运调节

在糖耐量异常、2型糖尿病患者及鼠模型的骨骼肌和脂肪组织中蛋白激酶B(PKB)的含量下降 ,其在胰岛素刺激下向细胞膜的转移量也明显降低。利用PKB抑制剂ML9或无酶活性及磷酸化缺陷的AAA Akt,可完全阻止鼠脂肪细胞或L6成肌细胞葡萄糖转运和葡萄糖转运子 4 (GLUT4 )易位。此外 ,氧化、渗透应激可抑制胰岛素刺激的PKB激活作用 ,该作用与胰岛素刺激的葡萄糖转运活性受损类似     

钒酸盐对糖尿病大鼠骨骼肌GLUT4基因表达的影响

观察钒酸欠对ＳＴＺ糖尿病大鼠糖代谢的影响地这一作用产生的机理进行了探讨。以０．５ｍｇ／ｍｌ钒酸钠溶液作为饮用水治疗三周后，糖尿病治疗组的血糖低于非治疗组３７．５％，但仍较正常组高。而骨骼肌中ＧＬＵＴ４ｍＲＮＡ含量较非治疗组高７３．８％，但仍代于正常组。     

Exercise training increases the activity of pyruvate dehydrogenase complex in skeletal muscle of diabetic rats

The effects of diabetes and exercise training on the activity of pyruvate dehydrogenase (PDH) complex in skeletal muscle were examined in rats. Male Sprague-Dawley rats were divided into four groups as follows: non-diabetic sedentary, non-diabetic trained, diabetic sedentary, and diabetic trained groups. Diabetic rats were prepared by a bolus injection of intravenous streptozotocin (50 mg/kg body weight). Exercise training was performed by having rats run on a treadmill at a speed of 25 m/min for 45 min/day, 6 days/wk for 4 wks. Exercise training decreased serum concentrations of glucose and non-esterified fatty acid in diabetic rats. GLUT4 content in skeletal muscle in sedentary rats was significantly decreased by diabetes; however, exercise training significantly increased the GLUT4 content in diabetic rats. The total and actual activities and the proportion of actual activity of the PDH complex were decreased in diabetic sedentary rats. Exercise training did not affect the total activity of the PDH complex in non-diabetic rats, whereas it increased the total activity in diabetic rats to the same level as that in non-diabetic rats. In diabetic rats, exercise training tended to increase the proportion of actual activity of the PDH complex from 2.7 +/- 0.4% to 4.7 +/- 0.8%, although the proportion of actual activity in non-diabetic rats was decreased by exercise training. The present study suggests that exercise training may improve glucose metabolism in the skeletal muscle of streptozotocin-induced diabetic rats probably through the mechanisms of increasing both GLUT4 content and the activity of the PDH complex.     

姜黄素促进骨骼肌GLUT4转位改善糖尿病大鼠胰岛素抵抗

目的:研究姜黄素对STZ诱导糖尿病大鼠骨骼肌胰岛素抵抗的影响及其机制。方法:雄性SD大鼠腹腔注射STZ诱导糖尿病大鼠模型。成模大鼠分为糖尿病组(DM),糖尿病＋姜黄素组(DM＋Cur),糖尿病＋缓冲液对照组(DM＋NC)。以正常SD大鼠为正常对照组(NC)。DM＋Cur组予姜黄素灌胃治疗,DM＋NC组给予等体积缓冲液灌...     

Effect of early insulin therapy on nuclear factor κB and cytokine gene expressions in the liver and skeletal muscle of high-fat diet,streptozotocin-treated diabetic rats

To clarify the effect of early insulin therapy on nuclear factor kappaB (NFkappaB) pathway and inflammatory cytokine responses in the liver and skeletal muscle in type 2 diabetes. High-fat diet and low dose streptozotocin (STZ) induced diabetic rats were given NPH insulin or gliclazide for 3 weeks initiated at the 3rd day after STZ injection as early treatment and NPH for 3 weeks at 1 month as late treatment. Intraperitoneal glucose tolerance test (IPGTT) was performed at 3rd day after the end of treatment. Early interventions caused a decrease in glucose-insulin index in IPGTT, promoted glucose transporter 4 (Glut4) gene and protein expressions in muscle and reduced phosphoenolpyruvate carboxykinase (PEPCK) protein levels in the liver. There was an increase in inhibitor kappaB (IkappaBalpha) protein and a decrease in NFkappaB p65 DNA binding activity. A decreased level in mRNAs encoding tumor necrosis factor (TNF)alpha in the liver and muscle and interleukin (IL)-1beta in the liver were observed. Our results suggested that early insulin treatment inhibits NFkappaB activity and inflammatory cytokine responses in the liver and skeletal muscle that were involved in the amelioration of insulin resistance in type 2 diabetic rats.     

Zanthoxylum alkylamides activate phosphorylated AMPK and ameliorate glycolipid metabolism in the streptozotocin-induced diabetic rats

This study aimed to evaluate the effects of Zanthoxylum alkylamides on the glycolipid metabolism of rats with streptozotocin (STZ)-induced diabetes. Diabetic rats were given daily oral treatments of 2, 4, or 8 mg/kg bw alkylamides for 28 days. Alkylamides significantly decreased fasting blood glucose and fructosamine content, as well as relieved organ enlargement caused by diabetes. The serum and liver triglyceride, malondialdehyde, and free fatty-acid contents of rats with STZ-induced diabetes were significantly reduced. Total cholesterol in the liver also significantly decreased. Quantitative polymerase chain reaction (Q-PCR) and Western blot detected insignificantly increased (P > 0.05) mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK) in the skeletal muscle of diabetic rats. However, AMPK and p-AMPK (Thr172) protein expression levels significantly increased. The mRNA and protein expression levels of silencing information regulator 1 significantly increased. The mRNA expression levels of acetyl-CoA-carboxylase (ACC) and protein p-ACC (Ser79) also increased. The mRNA and protein expression levels of glucose transporter type 4 (GLUT4) were significantly upregulated in the skeletal muscle cell membranes of diabetic rats. Results indicated that alkylamides activated the AMPK-signaling pathway. Thus, inhibiting ACC activity reduced fatty-acid synthesis. The rapid translocation of GLUT4 mediated increased glucose transport rate and reduced blood glucose. Therefore, alkylamides can ameliorate glucose and lipid metabolism disorders in diabetic rats by activating the AMPK pathway.     

薏苡仁多糖对实验性2型糖尿病大鼠胰岛素抵抗的影响

目的 观察薏苡仁多糖对实验性2型糖尿病大鼠胰岛素抵抗的影响。方法 用小剂量链脲佐菌素（25mg/kg,iv)加高热量饲料（热卡：20.083J/g)建立实验性2型糖尿病大鼠模型，然后用薏苡仁多糖分三个剂量组（25、50、100mg/kg，ip)给药治疗2周，并测定葡萄糖耐量，血浆胰岛素以及肝糖原、肌糖原、肝细胞膜胰岛素受体结合率和肝葡萄糖激酶活性。结果 薏苡仁多糖能改善实验性2型糖尿病大鼠糖耐量异常，增加肝糖原量和肝葡萄糖激酶活性，且呈现一定的量效关系。但对血浆胰岛素水平及胰岛素受体最大结合率和受体最大结合容量均无影响。结论 薏苡仁多糖能够改善实验性2型糖尿病大鼠胰岛素抵抗，这可能与其调节糖代谢酶的活性有关。     

Influence of streptozotocin-induced diabetes in rats on the lithium content of tissue and the effect of dietary lithium supplements on this diabetic condition.

To study the effects of lithium supplementation on the diabetic condition, we measured the lithium concentration in the liver, kidney, and muscle from streptozotocin (STZ)-induced diabetic male Sprague-Dawley (SD) rats that were either treated or untreated with peroral lithium carbonate (0.3 mg/mL). The data showed that the lithium content of the liver and muscle was significantly lower in STZ rats than in normal control rats (0.22 +/- 0.05 v 1.30 +/- 0.15, P < .01, and 0.79 +/- 0.30 v 2.48 +/- 2.00 microg/g, respectively). After 4 weeks of lithium carbonate supplementation, we found that (1) the lithium content of the liver and muscle returned to the normal range, (2) the extent of STZ-mediated destruction of beta cells in the pancreas decreased, (3) fasting blood glucose (FBG) and 2-hour postprandial blood glucose (PBG) decreased (P < .05), (4) among the indicators of oxidative stress and antioxidant defenses, blood lipid peroxidate (LPO) decreased and erythrocyte superoxide dismutase (RBC-SOD) and glutathione (GSH) returned to normal, and (5) hepatic LPO decreased and glutathione peroxidase (GSH-Px) increased. These results suggest that the restoration of lithium to control levels in the liver and muscle of diabetic animals is associated not only with decreased blood glucose but also with reduced oxidative stress, and consequently with the protection of insulin-secreting pancreatic islet cells.     

Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats

Adiponectin can improve both glucose metabolism and insulin resistance via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Activated AMPK phosphorylates a variety of intracellular proteins, including acetyl coenzyme A carboxylase (ACC) that is involved in fatty acid oxidation. Adenosine monophosphate-activated protein kinase increases glucose transport by stimulating the translocation of glucose transporter 4 (GLUT4) to the sarcolemma in the heart. Adiponectin exerts its effect through adiponectin receptors, which are predominantly expressed in the liver and skeletal muscle. It is unknown whether the cardiac expression of adiponectin and its receptors is changed in diabetic rats. In the present study, we investigated the protein expression of adiponectin and its receptors in streptozotocin (STZ)-induced diabetic rat hearts. We also explored whether the levels of AMPK, ACC, and GLUT4 will be altered with the changed adiponectin and its receptors in STZ diabetic rat hearts. Plasma and cardiac adiponectin levels were measured by radioimmunoassay. Plasma and cardiac interleukin 6 and plasma tumor necrosis factor alpha (TNF-alpha) were assayed by enzyme-linked immunosorbent assay. Cardiac adiponectin receptors, AMPK-alpha, ACC, GLUT4, and TNF-alpha were analyzed by Western blot in control and STZ diabetic rats. The plasma adiponectin level was decreased, but the cardiac protein expression of adiponectin receptor 1 was increased in diabetic rats. There was no difference in the cardiac adiponectin level and the cardiac adiponectin receptor 2 protein expression between control and diabetic rats. The phosphorylation of AMPK-alpha and protein expression of GLUT4 were decreased, but the phosphorylation of ACC was unchanged in diabetic rat hearts. Plasma and cardiac levels of interleukin 6 and TNF-alpha were increased in diabetic rats. In conclusion, STZ-induced diabetes up-regulates adiponectin receptors in the heart. Despite an increase in cardiac adiponectin receptor 1 expression, there is an increased cardiac inflammatory response and a decreased GLUT4 protein expression associated with a reduction in circulating adiponectin.     

Impaired insulin action despite upregulation of proximal insulin signaling: novel insights into skeletal muscle insulin resistance in liver cirrhosis

BACKGROUND/AIMS: Disturbance in glucose metabolism is a common feature in liver diseases and this is associated with skeletal muscle insulin resistance. However, the underlying molecular mechanisms are unclear. To characterize skeletal muscle insulin resistance associated with liver disease, we examined muscles from animals after an acute, 5 weeks perturbation of the common bile duct. Clinical findings, elevated plasma levels of liver enzymes and histological examinations confirmed cirrhosis. METHODS/RESULTS:: Cirrhotic animals were insulin resistant and this was associated with reduced glucose transport into muscles. Interestingly, activity in the proximal part of the insulin signaling cascade was not decreased, as evinced by increased activity of key enzymes in the signal to glucose transport. Expression of the glucose transporter, GLUT4, was normal. So together these results indicate that signaling downstream of PKB/Akt and/or the translocation of GLUT4 is impaired in skeletal muscle from cirrhotic animals. CONCLUSIONS: In conclusion, in an animal model of liver cirrhosis whole body insulin resistance is associated with insulin resistance in skeletal muscles. Unlike other common forms of insulin resistance, muscles from cirrhotic animals have increased activity in the proximal insulin signaling cascade. This emphasizes the fact that skeletal muscle insulin resistance associated with liver cirrhosis is a unique entity.