INABILITY TO STIMULATE SKELETAL-MUSCLE OR WHOLE-BODY PROTEIN-SYNTHESIS IN TYPE-1 (INSULIN-DEPENDENT) DIABETIC-PATIENTS BY INSULIN-PLUS-GLUCOSE DURING AMINO-ACID INFUSION - STUDIES OF INCORPORATION AND TURNOVER OF TRACER L-[1-C-13]LEUCINE
INABILITY TO STIMULATE SKELETAL-MUSCLE OR WHOLE-BODY PROTEIN-SYNTHESIS IN TYPE-1 (INSULIN-DEPENDENT) DIABETIC-PATIENTS BY INSULIN-PLUS-GLUCOSE DURING AMINO-ACID INFUSION - STUDIES OF INCORPORATION AND TURNOVER OF TRACER L-[1-C-13]LEUCINE
复制标题
DOI：
10.1007/bf00586460
复制
发表时间：
1990-01-01
期刊：
影响因子：
8.2
通讯作者：
RENNIE, MJ
中科院分区：
文献类型：
--
作者：
BENNET, WM;CONNACHER, AA;RENNIE, MJ
尽管胰岛素对蛋白质平衡有合成代谢作用，但据报道，急性注射胰岛素对人体骨骼肌或全身蛋白质合成没有影响。然而，胰岛素也会降低血浆和肌内氨基酸的利用率，这可能会限制蛋白质合成。因此，我们测量了 8 名停用胰岛素的 1 型（胰岛素依赖型）糖尿病患者中胰岛素对骨骼肌（胫骨前肌）蛋白质合成和全身亮氨酸周转的急性影响。他们最初是在胰岛素缺乏时进行研究的，但在以足以将血浆氨基酸提高30%（即总共4mmol/l）的速度输注混合氨基酸期间；当胰岛素与增加的氨基酸速率一起输注以维持胰岛素缺乏的血浆氨基酸浓度时，继续测量。使用血浆中的13C-α-酮异己酸作为细胞内前体标记的指标，[1-13C]亮氨酸掺入骨骼肌蛋白中为0.068±。胰岛素停药期间为 0.007%/h，胰岛素输注期间没有变化。该值高于健康人肌肉中观察到的值，可能是由于内源性肌内氨基酸的刺激作用。而且，根据α-酮异己酸标记计算，未氧化的全身亮氨酸消失(即全身蛋白质合成)为110±。 4.mu.mol.cntdot。 kg-1.cntdot.h-1 胰岛素停药期间：这在胰岛素输注期间也没有变化。 尽管大多数氨基酸的血浆浓度稳定或增加，但许多氨基酸的肌内浓度在胰岛素输注期间下降。这可能限制了胰岛素对蛋白质合成的任何合成代谢作用。或者，预先存在的高肌内氨基酸可能最大限度地刺激了肌肉蛋白质合成，因此进一步的升高被掩盖，特别是在前体氨基酸耗尽的趋势下。
Despite its anabolic effects on protein balance, acute administration of insulin has been reported to have no effect on skeletal muscle or whole body protein synthesis in man. However, insulin also reduces plasma and intramuscular amino acid availability, which may limit protein synthesis. We have therefore measured the acute effects of insulin on skeletal muscle (anterior tibialis) protein synthesis and whole body leucine turnover in eight insulin-withdrawn Type 1 (insulin-dependent) diabetic patients. They were studied initially when insulin deficient, but during infusion of mixed amino acids at a rate sufficient to raise plasma amino acids by 30% i.e. to 4 mmol/l in total; measurements were continued when insulin was infused together with an increased rate of amino acids to maintain insulinopoenic plasma amino acid concentrations. Using 13C-.alpha.-ketoisocaproate in plasma as an index of the intracellular precursor labelling, incorporation of [1-13C]leucine into skeletal muscle protein was 0.068 .+-. 0.007%/h during insulin withdrawal and was unaltered during insulin infusion. The value is higher than observed in muscle of healthy man, possibly because of a stimulatory effect of endogenous intramuscular amino acids. Also, calculated on the basis of .alpha.-ketoisocaproate labelling, nonoxidised whole body leucine disappearance (i.e. whole body protein synthesis) was 110 .+-. 4 .mu.mol .cntdot. kg-1.cntdot.h-1 during insulin withdrawal: this also was unchanged during insulin infusion. Despite stable or increased plasma concentrations of most amino acids, the intramuscular concentrations of a number of amino acids decreased during insulin infusion. This may have limited any anabolic effect of insulin on protein synthesis. Alternatively, pre-existing high intramuscular amino acids may have maximally stimulated muscle protein synthesis, so that the further elevation was obscured, especially with the tendency to depletion of precursor amino acids.