INSULIN AND PROTEIN SYNTHESIS AFTER RESISTANCE EXERCISE

抗阻运动后胰岛素和蛋白质的合成

• 批准号: 2390540
• 负责人: PETER A FARRELL
• 金额: $ 28.04万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 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/2390540
• 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

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.

该项目将检验胰岛素对于以下疾病至关重要的假设： 运动引起的蛋白质合成率和骨骼率的增加 肌肉肥大。胰岛素依赖型糖尿病会导致 骨骼肌质量加速损失。这种损失可以通过以下方式抵消 抗阻运动会导致蛋白质净增加，但是 胰岛素在这种沉积过程中的作用尚未得到系统研究。 具体目标：我们将确定蛋白质比率是否升高 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 肽链起始中的特定真核起始因子（ mRNA 翻译成蛋白质的第一步），以及调节 在II型骨骼肌纤维中更为明显。胰岛素可用性 运动期间和运动后对于增加蛋白质摄入量可能至关重要 抗阻运动后合成。然后我们将确定是否 胰岛素注射的大鼠肌肉肥大的能力受到损害 缺陷以及这种减少是否是由于监管的改变 肽链起始的具体步骤。实验和方法：大鼠 习惯于用后肢站起来并按下开关 对灯光提示做出反应（以避免触电）。添加了阻力 在 Velcro 背心上使用重量包（重量超过肩胛骨）。急性 阻力训练将是为期 4 天的举重训练。 慢性抵抗运动将持续 3、6 或 9 周，并逐渐进行 背包上增加了更大的重量 低胰岛素血症对增加蛋白质合成速率的能力的影响 剧烈运动后以及由于以下原因导致肌肉肥大的能力 长期运动将使用 70% 和 90% 部分来阐明 成熟大鼠（250g）的胰腺切除术。蛋白质合成速率为 通过使用体内 3H-苯丙氨酸的掺入来测量 氚化苯丙氨酸驱替剂量技术或原位双侧 急性或慢性运动后16小时后肢灌注。因为 胰岛素对肽链起始的影响在 快肌纤维，我们将比较和对比分级的影响 腓肠肌（主要是 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 II型，但在演习期间并未广泛招募）。变化 第435章 核糖体聚集和形成预起始的能力 单个肌肉中的复合体将被用作变化的标记 肽链起始。拟议的参与机制 肽链起始将通过测量的表达来评估 真核起始因子 2B (eIF-2B) 和 eIF-4E，eIF- 的活性 图2B和eIF-4E的磷酸化状态。意义：拟议的研究 将是第一个系统评估胰岛素在蛋白质中的作用的人 蛋白质净增加期间的合成。我们预测一个关键的 胰岛素在调节运动诱发的纤维中的特异性作用 肥大。