REGULATION OF PROTEIN TURNOVER IN DIABETIC HEART

这个项目的目标是检验假设， 糖尿病心脏的蛋白质合成和降解率部分 通过加速吸收非碳水化合物底物，如脂肪 酸、酮体和支链氨基酸。 蛋白质的恢复 合成涉及加速肽链起始。 机制 恢复正常的降解速率似乎不太有效。 提供 脂肪酸和氨基酸都能抑制降解，但效果不佳 作为胰岛素。 更快的降解，以及数量的限制 可用于合成的核糖体的减少，将导致 一些心脏蛋白质，并可能损害组织的功能。 这一假设将通过确定调节 正常和糖尿病大鼠心脏中的肽链起始， 这些因素对维持启动的贡献， 胰岛素缺乏组织。 将通过测量 苯丙氨酸在放线菌酮存在和不存在下的释放。 率 释放将与溶酶体酶的潜伏期相关。 率 在分离的灌注大鼠心脏中测量合成和降解。 这些速率将通过改变灌注液中游离脂肪酸的水平而变化， 酮体、氨基酸和胰岛素。 这些研究表明， 维持糖尿病动物心脏功能的方法。

The goal of this project is to examine the hypothesis that the balance between rates of protein synthesis and degradation in diabetic hearts is partially restored by accelerated uptake of non-carbohydrate substrates such as fatty acids, ketone bodies and branched-chain amino acids. Restoration of protein synthesis involves acceleration of peptide-chain initiation. Mechanisms to restore normal rates of degradation appear to be less effective. Provision of both fatty acids and amino acids restrains degradation, but not as effectively as insulin. More rapid degradation, together with a restriction in the number of ribosomes available for synthesis, would lead to a reduction in the levels of some heart proteins and may impair function of the tissue. This hypothesis will be examined by identifying the factors regulating peptide-chain initiation in hearts of normal and diabetic rats and by evaluating the contribution of these factors to maintenance of initiation in insulin-dificient tissue. Protein degradation will be assessed by measuring release of phenylalanine in the presence and absence of cycloheximide. Rates of release will be correlated with latency of lysosomal enzymes. Rates of synthesis and degradation will be measured in the isolated perfused rat heart. These rates will be varied by changing perfusate levels of free fatty acids, ketone bodies, amino acids and insulin. These studies should suggest new approaches to maintaining heart function in diabetic animals.