Yamasaki H, Akazawa S, Okuno S, Ikari N, Yamaguchi Y, Chikuba N, Yamamoto H, Maeda Y, Tahara D, Nagataki S
First Department of Internal Medicine, Nagasaki University, School of Medicine, Japan.
Diabetes Res Clin Pract. 1992 Feb;15(2):105-11. doi: 10.1016/0168-8227(92)90013-h.
Werner's syndrome is a genetic disease characterized by premature aging and is often associated with glucose intolerance due to insulin resistance. The clinical manifestations in this syndrome are preferentially expressed in the face and acral regions without apparent involvement of the trunk. We compared insulin receptor binding and amino acid uptake of fibroblasts derived from the forearm that had sclerodermoid features, and from the abdomen that was apparently normal in a patient with Werner's syndrome. In normal controls, specific insulin binding was not different in forearm and abdomen-derived fibroblasts (10.72 +/- 2.11%, 10.40 +/- 1.27%, respectively). In the patient, however, specific insulin binding was reduced in the fibroblasts derived from the forearm compared with those derived from the abdomen (3.55%, 8.16%, respectively). Scatchard analysis revealed that the reduction in insulin binding of the forearm fibroblasts from the patient was due to a reduction in receptor number with no change in receptor affinity. The dose-response curve for insulin of alpha-aminoisobutyric acid (AIB) uptake is shifted to the right in the fibroblasts derived from the acral area. The results show that in a patient with Werner's syndrome, regional differences occur in fibroblast insulin receptor binding and function. This suggests early phenotypic expression of the genetic abnormality of insulin receptor function in these patients.
沃纳综合征是一种以早衰为特征的遗传性疾病，常因胰岛素抵抗而伴有葡萄糖不耐受。该综合征的临床表现优先表现在面部和肢端区域，躯干无明显受累。我们比较了一名沃纳综合征患者前臂硬皮病样特征的成纤维细胞和腹部明显正常的成纤维细胞的胰岛素受体结合及氨基酸摄取情况。在正常对照组中，前臂和腹部来源的成纤维细胞的特异性胰岛素结合无差异（分别为10.72±2.11%、10.40±1.27%）。然而，在该患者中，前臂来源的成纤维细胞的特异性胰岛素结合与腹部来源的相比降低（分别为3.55%、8.16%）。Scatchard分析显示，患者前臂成纤维细胞胰岛素结合减少是由于受体数量减少，受体亲和力无变化。肢端区域来源的成纤维细胞中，α-氨基异丁酸（AIB）摄取的胰岛素剂量-反应曲线向右移动。结果表明，在沃纳综合征患者中，成纤维细胞胰岛素受体结合和功能存在区域差异。这提示这些患者胰岛素受体功能的遗传异常存在早期表型表达。
