Ramachandran A, Susheela L, Mohan V, Kuzhali D A, Viswanathan M
Diabetes Research Centre, Royapuram, Madras, India.
Diabetes Res Clin Pract. 1988 Oct 14;5(4):241-7. doi: 10.1016/s0168-8227(88)80058-5.
Insulin binding to erythrocyte insulin receptors was studied in 23 offspring (13 men and 10 women) born of conjugal diabetic parents having type 2 diabetes. Nine of the offspring were obese and 14 were non-obese, but all had normal glucose tolerance. Twenty-three age-, sex- and weight-matched non-diabetic subjects without a family history of diabetes were studied as controls. In the non-obese offspring mean basal plasma immunoreactive insulin (IRI) was elevated (P less than 0.01), but the mean stimulated IRI showed no change in comparison to that of controls. In the obese offspring mean basal plasma IRI was similar, but the mean stimulated IRI was lower than that of obese controls (P less than 0.01). Mean specific insulin binding was decreased in both obese (P less than 0.01) and non-obese (P less than 0.01) offspring when compared with the respective controls. Scatchard analysis of the binding data and the higher insulin concentrations required to achieve 50% inhibition of tracer binding indicated decreased receptor affinity in both obese and non-obese offspring. Analysis by average affinity profiles also indicated decreased receptor affinity, as shown by a lower average affinity constant Kc for the empty sites, in the offspring in comparison to that of controls (P less than 0.001). Abnormalities in insulin binding to its receptor along with decreased affinity in the face of normal glucose tolerance may be an early biochemical marker of potential diabetes in this group at high risk of developing diabetes.
对23名患有2型糖尿病的已婚糖尿病患者所生的后代（13名男性和10名女性）的红细胞胰岛素受体上胰岛素结合情况进行了研究。其中9名后代肥胖，14名不肥胖，但所有人的糖耐量均正常。选取23名年龄、性别和体重匹配且无糖尿病家族史的非糖尿病受试者作为对照。在非肥胖后代中，基础血浆免疫反应性胰岛素（IRI）均值升高（P<0.01），但与对照组相比，刺激后的IRI均值无变化。在肥胖后代中，基础血浆IRI均值相似，但刺激后的IRI均值低于肥胖对照组（P<0.01）。与各自的对照组相比，肥胖后代（P<0.01）和非肥胖后代（P<0.01）的平均特异性胰岛素结合均降低。对结合数据进行Scatchard分析以及实现50%放射性示踪剂结合抑制所需的更高胰岛素浓度表明，肥胖和非肥胖后代的受体亲和力均降低。通过平均亲和力曲线分析也表明后代的受体亲和力降低，与对照组相比空位点的平均亲和力常数Kc较低（P<0.001）。在糖耐量正常的情况下，胰岛素与其受体结合异常以及亲和力降低可能是该糖尿病高危人群潜在糖尿病的早期生化标志物。
