THE INDUCTION OF A SPECIFIC PROTEASE FOR INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 IN THE CIRCULATION DURING SEVERE ILLNESS
THE INDUCTION OF A SPECIFIC PROTEASE FOR INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 IN THE CIRCULATION DURING SEVERE ILLNESS
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DOI：
10.1677/joe.0.1300469
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发表时间：
1991-09-01
影响因子：
4
通讯作者：
HOLLY, JMP
中科院分区：
文献类型：
--
作者：
DAVIES, SC;WASS, JAH;HOLLY, JMP
胰岛素样生长因子（IGF-I和IGF-II）在循环中几乎完全结合到特异性结合蛋白（IGFBPs）。 这些IGFBPs似乎在维持循环水平和调节IGF向组织的递送中起关键作用。 大部分的循环IGF以高亲和力结合于结合蛋白之一IGFBP-3。 这些IGF从循环池转移到组织受体的机制目前尚不清楚。 最近的研究表明，在妊娠后期的特定蛋白酶的存在下，可能会修改IGFBPs，使他们的亲和力的IGFs降低。 在本文中，我们已经证明了存在一种热敏感的阳离子依赖性蛋白水解酶特异性IGFBP-3在血清中的5个严重的病人。 发现这种蛋白酶的活性在这些患者中变化，在禁食期间比在开始肠外营养后研究时变得更明显，表明这种蛋白酶活性的影响因素之一是患者的营养摄入。 年龄和性别匹配的健康成人也进行了研究，在一个类似的协议，但没有任何IGFBPs的蛋白水解修饰被发现在任何检查的样品。 由于IGF-I和IGF-II的水平在患者中被发现是低的，循环蛋白酶的存在表明，这可能是一种适应性反应，以增加IGFs的生物利用度，并可能改善氮潴留和对抗严重疾病中的分解代谢状态。
The insulin-like growth factors (IGF-I and IGF-II) are almost completely bound in the circulation to specific binding proteins (IGFBPs). These IGFBPs appear to play a pivotal role in maintaining circulating levels and modulating the delivery of the IGFs to the tissues. A large proportion of the circulating IGFs are bound with high affinity to one of the binding proteins, IGFBP-3. The mechanism by which these IGFs are transferred from the circulatory pool to the tissue receptors is at present unclear. Recent studies in late pregnancy have demonstrated the presence of specific proteases which may modify the IGFBPs such that their affinities for the IGFs are reduced. In this paper, we have demonstrated the presence of a heat-sensitive cation-dependent proteolytic enzyme specific for IGFBP-3 in the serum of five severely ill patients. The activity of this protease was found to vary in these patients, becoming more apparent during fasting than when studied after commencement of parenteral nutrition, indicating that one of the influencing factors in the activity of this protease is the nutritional intake of the patient. Age- and sex-matched healthy adults were also studied in a similar protocol, but no proteolytic modification of any of the IGFBPs was found in any of the samples examined. As the levels of both IGF-I and IGF-II were found to be low in the patients, the presence of a circulatory protease suggests that this may be an adaptive response to increase the bioavailability of the IGFs and possibly to improve the nitrogen retention and counter the catabolic state in severe illness.