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INSULIN AND PROTEIN SYNTHESIS AFTER RESISTANCE EXERCISE

抗阻运动后胰岛素和蛋白质的合成

基本信息

批准号：
2899890
负责人：
PETER A FARRELL
金额：
$ 26.94万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-04-20 至 2000-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2899890
关键词：
diabetes mellitus disease /disorder model exercise gastrocnemius muscle hormone regulation /control mechanism insulin laboratory rat muscle hypertrophy operant conditionings pancreatectomy phenylalanine protein biosynthesis ribosomes translation factor

项目摘要

This project will examine the hypothesis that insulin is critical for exercise-induced increases in rates of protein synthesis and skeletal muscle hypertrophy. Insulin Dependent Diabetes Mellitus causes an accelerated loss of skeletal muscle mass. This loss may be counteracted by resistance exercise which results in net protein accretion, however the role of insulin during such accretion has not been systematically studied. Specific Aims: We will determine whether elevations in rates of protein synthesis after acute and chronic resistance exercise are due to insulin- dependent increases in peptide-chain initiation. Insulin regulates specific eukaryotic initiation factors in peptide-chain initiation (the first steps in the translation of mRNA into protein), and that regulation is more pronounced in type II skeletal muscle fibers. Insulin availability during and after exercise may be critical for increasing rates of protein synthesis after resistance exercise. We will then determine whether the ability of muscle to hypertrophy is compromised in rats rendered insulin- deficient and whether such a decrement is due to altered regulation of specific steps in peptide chain initiation. Experiments and Methods: Rats are conditioned to rise up on their hindlimbs and push a switch in response to a light cue (to avoid electric shock). Resistance is added using weight packs on a Velcro vest (weights over the scapula). Acute resistance exercise will be weight lifting sessions on 4 separate days. Chronic resistance exercise will last 3, 6 or 9 wks with progressively greater weights being added to the backpacks The effect of prevailing hypoinsulinemia on the ability to increase rates of protein synthesis after acute exercise and the ability of muscle to hypertrophy due to chronic exercise will be elucidated using 70 and 90% partial pancreatectomy of mature (250g) rats. Rates of protein synthesis will be measured by incorporation of 3H-Phenylalanine using either an in vivo tritiated phenylalanine flooding dose technique or in situ bilateral hindlimb perfusion 16 hr after acute or chronic exercise. Because the effects of insulin on peptide-chain initiation are more pronounced in fast-twitch fibers, we will compare and contrast the affects of graded insulinemia on gastrocnemius (predominantly Type II), soleus (predominantly Type I), and extensor digitorum longus (EDL, predominantly Type II, but not extensively recruited during the exercise). Changes in ribosomal aggregation and the ability to form the 435 preinitiation complex in individual muscles will be used as markers of alterations in peptide-chain initiation. Mechanisms of the proposed involvement of peptide chain initiation will be evaluated by measuring the expression of eukaryotic initiation factor 2B (eIF-2B) and eIF-4E, the activity of eIF- 2B and phosphorylation state of eIF-4E. Significance: The proposed studies will be the first to systematically assess a role for insulin in protein synthesis during periods of net protein accretion. We predict a critical and fiber-specific role for insulin in mediating exercise-induced hypertrophy.

本项目将研究胰岛素对胰岛素依赖性的假设。运动引起的蛋白质合成率和骨骼肌肌肉肥大胰岛素依赖型糖尿病是一种骨骼肌质量的加速损失。这种损失可以通过以下方式抵消：抗阻运动导致净蛋白质增加，然而，胰岛素在这种增生过程中的作用尚未得到系统的研究。具体目标：我们将确定蛋白质摄入率的升高是否急性和慢性抵抗运动后的合成是由于胰岛素- 肽链起始的依赖性增加。胰岛素调节在肽链起始中的特异性真核起始因子（ mRNA翻译成蛋白质的第一步），而这种调节在II型骨骼肌纤维中更为明显。胰岛素利用率在运动期间和运动后，抗阻运动后的合成。然后我们将确定在给予胰岛素的大鼠中，肌肉肥大的能力受到损害，是否有缺陷，以及这种减少是否是由于改变了监管肽链起始的特定步骤。实验和方法：大鼠习惯于用后肢站立，对光线的反应（避免电击）。阻力增加使用尼龙搭扣背心上的重量包（肩胛骨上的重量）。急性阻力运动将是举重会议在4个独立的天。慢性抗阻运动将持续3、6或9周，更大的重量被添加到背包的影响，低胰岛素血症对增加蛋白质合成速率的能力急性运动后，由于肌肉的能力肥大，慢性运动将阐明使用70和90%的部分成熟（250 g）大鼠的胰腺切除术。蛋白质合成的速率将是通过使用体内掺入3 H-苯丙氨酸来测量，氚化苯丙氨酸泛液剂量技术或原位双侧急性或慢性运动后16小时后肢灌流。因为胰岛素对肽链起始的影响在以下情况下更明显：快缩纤维，我们将比较和对比的影响，腓肠肌（主要为II型）、比目鱼肌胰岛素血症（主要是I型）和趾长伸肌（EDL，主要是第二类，但在演习期间没有广泛招募）。变化核糖体聚集和形成435前起始的能力个体肌肉中的复合物将被用作肽链起始。拟议的参与机制肽链起始将通过测量真核起始因子2B（eIF-2B）和eIF-4 E，eIF-4 E的活性， 2B和eIF-4 E的磷酸化状态。意义：拟议的研究将是第一个系统地评估胰岛素在蛋白质中的作用，在蛋白质净增长期间进行合成。我们预测，胰岛素在介导运动诱导的肥厚