FAMILIAL HYPERPROINSULINEMIA DUE TO A PROPOSED DEFECT IN CONVERSION OF PROINSULIN TO INSULIN
FAMILIAL HYPERPROINSULINEMIA DUE TO A PROPOSED DEFECT IN CONVERSION OF PROINSULIN TO INSULIN
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DOI：
10.1056/nejm198409063111003
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发表时间：
1984-01-01
影响因子：
158.5
通讯作者：
SCHWARTZ, R
中科院分区：
文献类型：
--
作者：
GRUPPUSO, PA;GORDEN, P;SCHWARTZ, R
家族性高胰岛素原血症是一种遗传性疾病，其特征是血浆胰岛素原样物质水平升高。在2个先前描述的激酶，这被证明是由于在胰岛素原分子的结构异常。第三个家庭与高胰岛素原血症，其中似乎有一个不同的缺陷被确定。先证者是一名12岁的女孩，在口服葡萄糖耐量试验中有临界葡萄糖耐受不良和明显升高的免疫反应性胰岛素水平。血浆的凝胶过滤显示，66%的循环胰岛素免疫反应性是由胰岛素原样成分。4个兄弟姐妹中的两个，父亲和祖父在血糖浓度正常和胰岛素原样物质水平升高的情况下，空腹胰岛素免疫反应性也升高。在体外胰蛋白酶消化的血浆胰岛素原样物质从受影响的家庭成员显示，胰岛素原转化为胰岛素的方式与在控制。同样，胰岛素原和胰岛素在放射受体测定中表现出正常活性。胰岛素原分子在这个家庭显然是正常的，高胰岛素原血症是由于胰岛素原转化为胰岛素的缺陷。
Familial hyperproinsulinemia is a genetic disorder characterized by elevated plasma levels of proinsulin-like material. In 2 previously described kindreds this was shown to be due to a structural abnormality in the proinsulin molecule. A 3rd family with hyperproinsulinemia in which there appeared to be a different defect was identified. The propositus, a 12-yr-old girl, had borderline glucose intolerance and markedly elevated immunoreactive-insulin levels on oral glucose-tolerance testing. Gel filtration of plasma revealed that 66% of circulating insulin immunoreactivity was accounted for by the proinsulin-like components. Two of 4 siblings, the father, and the paternal grandfather also had elevated fasting insulin immunoreactivity in the presence of normal plasma glucose concentrations and elevated levels of proinsulin-like material. In vitro tryptic digestion of plasma proinsulin-like material from an affected family member revealed that proinsulin was converted to insulin in a manner indistinguishable from that in the control. Similarly, proinsulin and insulin exhibited normal activity in a radioreceptor assay. The proinsulin molecule in this family was apparently normal and hyperproinsulinemia was due to a defect in the conversion of proinsulin to insulin.