Studies on the pathogenesis of diabetes mellitus, with special reference to the abnormality of insulin secretion.

1)糖尿病患者父母的糖耐量和胰岛素反应：对44例年轻糖尿病患者的父母进行100 g葡萄糖耐量试验。2型糖尿病患者的父母中葡萄糖耐受不良的发生率明显更高（糖尿病和糖耐量受损：1型糖尿病患者分别为9%和9%，2型糖尿病患者分别为39%和12%）。在1型和2型患者的父母中，低胰岛素应答者的频率分别为43%和66%，在糖耐量正常的父母中，分别为33%和35%。在2型糖尿病患者中，父母双方通常都有低胰岛素反应（58%），而在1型糖尿病患者中，大多数只有父母一方有低胰岛素反应（58%），而在1型糖尿病患者中，大多数只有父母一方有低胰岛素反应（67%）。因此，低胰岛素反应似乎是两种糖尿病的遗传基础，但两种糖尿病的遗传方式可能不同。2）一个异常胰岛素血症家系的分析： ...更多信息 在先证者胰腺组织活检提取物中，正常胰岛素以等摩尔比存在。异常胰岛素的代谢比正常胰岛素慢，导致异常胰岛素在血液中蓄积、高胰岛素血症和异常与正常的高比率。氨基酸分析显示，异常胰岛素中A-3缬氨酸被亮氨酸取代。人胰岛素原的分泌：6只豚鼠用人胰岛素原免疫后，1只豚鼠产生胰岛素原特异性抗血清。用该抗血清建立了灵敏、特异的放射免疫分析方法。未经治疗的糖尿病患者空腹胰岛素原水平及其与胰岛素的比值升高。轻中度糖尿病患者糖负荷后胰岛素原分泌增强。糖尿病中胰岛素原的高比例可能代表了未成熟β颗粒从过度刺激的胰岛素分泌储备差的胰岛中动员的状态。少

1) Glucose tolerance and insulin response in parents of diabetic patients: Parents of 44 diabetic patients, whose diabetes developed at young ages, were examined by 100 g glucose tolerance test. Glucose intolerance was significantly more frequent in parents of type 2 diabetics (diabetes and impaired glucose tolerance: 9% and 9% in type 1, and 39% and 12% in type 2 diabetics, respectively). The frequency of low insulin responder was 43% and 66% in parents of type 1 and type 2 patients, and 33% and 35% in parents with normal glucose tolerance, respectively. In type 2 diabetics, both parents often had low insulin response (58%), while in type 1, mostly only one parents had low insulin response (58%), while in type 1, mostly only one parent had low insulin response (67%). Thus, low insulin response seems to have here-ditary basis for both types of diabetes, but the mode of inheritance probably differs between two types of diabetes.2) Analysis of a family of abnormal insulinemia: Abnormal a … More nd normal insulins existed in a equimolar ratio in the extract of a pancreatic tissue biopsied from the proband. Abnormal insulin was metabolized slower than normal insulin, resulting in the accumulation of abnormal insulin in blood, hyperinsulinemia and a high abnormal to normal ratio. Amino acid analysis revealed that A-3 valine was replaced by leucine in abnormal insulin. Urinary clearance of abnormal insulin was found to be extremely lower than normal insulin.3) The secretion of human proinsulin: Among 6 guinea pigs immunized with human proinsulin, one yielded proinsulin-specific antiserum. With this antiserum, a sensitive and specific radioimmunoassay was established. Fasting level of proinsulin and its ratio to insulin were elevated in untreated diabetic patients. The proinsulin secretion after glucose load was enhanced in patients with mild to moderate diabetes. The high proportion of proinsulin in diabetes may represent a state of mobilization of immature beta granules from over-stimulated islets with poor insulin secretory reserve. Less