Protein metabolism in clinically stable adult cystic fibrosis patients with abnormal glucose tolerance
Protein metabolism in clinically stable adult cystic fibrosis patients with abnormal glucose tolerance
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DOI：
10.2337/diabetes.50.6.1336
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发表时间：
2001-06-01
期刊：
影响因子：
7.7
通讯作者：
Nair, KS
中科院分区：
文献类型：
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作者：
Moran, A;Milla, C;Nair, KS
据报道，囊性纤维化(CF)患者会经历慢性蛋白质分解代谢。由于糖尿病或糖耐量受损(IGT)在CF中很常见，我假设他们的蛋白质分解代谢状态与胰岛素分泌减少或胰岛素作用减少有关。12名临床稳定、糖耐量异常的成人CF患者和12名年龄、性别和瘦体重匹配的健康对照组接受了蛋白质周转研究，分别使用L-[L-C-13]亮氨酸、L-[N-15]苯丙氨酸和L-[H-2(4)]酪氨酸，并分别给予和不给予外源性胰岛素输注。在基线空腹状态下，CF患者的蛋白质代谢完全正常，没有证据表明蛋白质分解代谢增加。相反，只有在注射胰岛素的CF患者中才能看到显著的异常，因为他们没有经历亮氨酸、苯丙氨酸或酪氨酸(蛋白质分解的指标)出现率的正常抑制。在胰岛素浓度为45+/-2MU/ml时，正常对照组亮氨酸出现率下降19+/-5%(P<；0.01)，酮异戊酸出现率下降103%(P=0.03)，酪氨酸出现率下降11+/-2%(P=0.03)，苯丙氨酸出现率下降6+/-3%(P=0.07)。苯丙氨酸到酪氨酸的转化率下降了22+/-7%(P=0.03)。在相似的胰岛素浓度为44+/-3Muu/ml时，CF中没有出现正常的氨基酸抑制现象。亮氨酸出现率下降4+/-2%(P=0.65)，酮异戊酸出现率下降1+/-2%(P=0.94)，酪氨酸出现率下降0+/-6%(P=0.56)，苯丙氨酸出现率下降5+/-6%(P=0.34)，苯丙氨酸转化率下降5+/-6%(P=0.95)。CF中氨基酸出现率抑制差与先前报道的糖耐量状态(IGT或无空腹高血糖的CF相关糖尿病)、空腹胰岛素水平、急性胰岛素反应、胰岛素敏感性、细胞因子或逆调节激素水平、静息能量消耗、卡路里摄入量、肺功能或临床状态无关。无论是正常对照组还是CF患者，胰岛素输注对蛋白质合成均无显著影响。综上所述，临床稳定的成人CF患者在禁食状态下蛋白质分解和合成指标正常。相比之下，将血浆胰岛素提高到餐后生理水平通常不能抑制蛋白质分解的指标。因此，在这些患者中蛋白质分解代谢的原因很可能是在餐后状态下缺乏多余的蛋白质。
Cystic fibrosis (CF) patients are reported to experience chronic protein catabolism. Since diabetes or impaired glucose tolerance (IGT) is common in CF, me hypothesized that their protein catabolic state is related to reduced insulin secretion or reduced insulin action. A total of 12 clinically stable adult CF patients with abnormal glucose tolerance and 12 age-, sex-, and lean body mass-matched healthy control subjects underwent protein turnover studies using L-[l-C-13]leucine, L-[N-15] phenylalanine, and L-[H-2(4)]tyrosine, with and without exogenous insulin infusion. In the baseline fasting state, protein metabolism was entirely normal in CF patients, with no evidence of increased protein catabolism. In contrast, striking abnormalities mere seen in CF patients when insulin was infused, since they did not experience normal suppression of the appearance rates of leucine, phenylalanine, or tyrosine (indexes of protein breakdown). At an insulin concentration of 45 +/- 2 muU/ml, normal control subjects suppressed the leucine appearance rate by 19 +/- 5% (P < 0.01), ketoisocaproate appearance rate by 10 3% (P = 0.03), tyrosine appearance rate by 11 +/- 2% (P = 0.03), and phenylalanine appearance rate by 6 +/- 3% (P = 0.07). Phenylalanine conversion to tyrosine decreased by 22 +/- 7% (P = 0.03). At a similar insulin concentration of 44 +/- 3 muU/ml, normal suppression of amino acid appearance did not occur in CF. The leucine appearance rate decreased by 4 +/- 2% (P = 0.65), ketoisocaproate appearance rate by 1 +/- 2% (P = 0.94), tyrosine appearance rate by 0 +/- 6% (P = 0.56), phenylalanine appearance rate by 5 +/- 6% (P = 0.34), and phenylalanine conversion to tyrosine by 5 +/- 6% (P = 0.95). poor suppression of the amino acid appearance rate in CF was not related to previously documented glucose tolerance status (IGT or CF-related diabetes without fasting hyperglycemia), fasting insulin levels, the acute insulin response, insulin sensitivity, cytokine or counterregulatory hormone levels, resting energy expenditure, caloric intake, pulmonary function, or clinical status. Protein synthesis was not significantly affected by insulin infusion in either normal control subjects or CF patients. In conclusion, clinically stable adult CF patients have normal indexes of protein breakdown and synthesis in the fasting state. In contrast, elevation of plasma insulin to physiological postprandial levels fails to normally suppress indexes of protein breakdown. It is therefore likely that inability to spare protein during the postprandial state is the cause of protein catabolism in these patients.