链脲佐菌素糖尿病大鼠骨骼肌蛋白周转增加与高浓度支链氨基酸有关

Teresa Rodrı́guez, Belén Alvarez, Sı́lvia Busquets, Neus Carbó, Francisco J. López-Soriano, Josep M. Argilés
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引用次数: 51

摘要

实验性链脲佐菌素诱导的糖尿病导致体重发生重大变化,这与水和食物摄入异常有关。此外,糖尿病大鼠表现出明显的肌肉萎缩,包括骨骼肌大小和蛋白质含量的减少。这伴随着胴体总氮的显著损失。这些变化与骨骼肌中蛋白质周转的重要改变有关。因此,糖尿病动物在合成(下降37%)和降解(增加140%)的分数蛋白率上都表现出变化。在糖尿病动物肌肉中观察到的蛋白质降解增加与循环氨基酸和肌肉氨基酸浓度的重要变化有关。有趣的是,尽管肾脏肿块明显增加(超过50%),但糖尿病动物的肝脏或肾脏蛋白质周转率均未出现重大变化。此外,虽然总氨基酸浓度不受糖尿病状态的影响,但化学诱导的糖尿病动物血液和骨骼肌中的支链氨基酸(亮氨酸、异亮氨酸和缬氨酸)均显著升高。同样,血液中谷氨酸+谷氨酰胺、丙氨酸、甘氨酸、脯氨酸、丝氨酸和苏氨酸的浓度也显著降低。这些观察结果强化了我们小组先前提出的肌肉蛋白质消耗、蛋白质周转增加和支链氨基酸改变之间的联系。
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The Increased Skeletal Muscle Protein Turnover of the Streptozotozin Diabetic Rat Is Associated with High Concentrations of Branched-Chain Amino Acids

Experimental streptozotozin-induced diabetes resulted in important changes in body weight which were associated with abnormalities in water and food intake. In addition, diabetic rats showed a clear muscle atrophy involving a decrease in both skeletal muscle size and protein content. This was accompanied by a marked loss of total carcass nitrogen. These changes were related to important alterations in protein turnover in skeletal muscle. Thus, the diabetic animals showed changes in the fractional protein rates of both synthesis (decreased by 37%) and degradation (increased by 140%). The increased protein degradation observed in the muscle of the diabetic animals was associated with important changes in the concentration of both circulating and muscle amino acids. Interestingly, the diabetic animals did not show important changes in either liver or kidney protein turnover rates, in spite of having a clear increase (over 50%) in kidney mass. In addition, and although the total amino acid concentration was not affected by the diabetic state, the chemically induced diabetic animals showed important elevations of branched-chain amino acids (leucine, isoleucine, and valine) in both blood and skeletal muscle. Similarly, important decreases in the blood concentrations of glutamate + glutamine, alanine, glycine, proline, serine, and threonine were also observed. These observations reinforce the idea of the association between muscle protein wasting, increased protein turnover, and alterations in branched-chain amino acids previously proposed by our group.

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