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

研究糖尿病发病机制，特别是胰岛素分泌异常。

• 批准号: 60480276
• 负责人: KUZUYA Takeshi
• 金额: $ 2.88万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480276/
• 关键词: Type 1 diabetes mellitus; Type 2 diabetes mellitus; Insulin secretion; Abnormal insulinemia; Proinsulin secretion; Family history; 糖負荷試験

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

1)糖尿病患者父母的糖耐量及胰岛素反应：对44例年轻时发病的糖尿病患者的父母进行100 g糖耐量试验。葡萄糖耐受不良在2型糖尿病患者的父母中更为常见（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%）。1型和2型患者的父母胰岛素应答低的频率分别为43%和66%，糖耐量正常的父母胰岛素应答低的频率分别为33%和35%。在2型糖尿病患者中，父母双方通常都有较低的胰岛素反应（58%），而在1型糖尿病患者中，通常只有父母一方有较低的胰岛素反应（58%），而在1型糖尿病患者中，通常只有父母一方有较低的胰岛素反应（67%）。因此，两种类型的糖尿病似乎都有低胰岛素反应的饮食基础，但两种类型的糖尿病之间的遗传模式可能不同。2) 1例胰岛素异常血症家族分析：先证者胰腺组织活检液中胰岛素异常多于正常，呈等摩尔比存在。异常胰岛素代谢慢于正常胰岛素，导致异常胰岛素在血液中积累，高胰岛素血症，异常正常比高。氨基酸分析显示异常胰岛素中A-3缬氨酸被亮氨酸取代。尿中异常胰岛素清除率明显低于正常胰岛素清除率。3)人胰岛素原分泌：用人胰岛素原免疫的6只豚鼠中，1只产生胰岛素原特异性抗血清。利用该抗血清，建立了一种灵敏、特异的放射免疫测定方法。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、中度糖尿病患者葡萄糖负荷后胰岛素原分泌增强。胰岛素原在糖尿病中的高比例可能代表了未成熟β颗粒从胰岛素分泌储备不足的过度刺激的胰岛中动员的状态。少

项目成果

Iwamoto, Yasuhiko: "A new case of abnormal insulinemia with diabetes. Reduced insulin values determined by radioreceptor assay." Diabetes. 35. 1237-1242 (1986)

Iwamoto，Yasuhiko：“糖尿病异常胰岛素血症的新病例。通过放射受体测定确定胰岛素值降低。”

Kuzuya, Takeshi: "Pathogenesis of type 2 diabetes mellitus." Progress in Diabetology. 20. 12-21 (1986)

Kuzuya, Takeshi：“2 型糖尿病的发病机制。”

岩本安彦: 糖尿病. 28. 1435-1436 (1985)

岩本泰彦：糖尿病。28. 1435-1436 (1985)

山本律子: Peptide Hormones. 6. 181-186 (1986)

山本律子：肽激素。6. 181-186 (1986)

Matsuda, Ayako: "Clinical features of adult-onset type 1 diabetes." J. Jpn. Diab. Soc.28. 1331-1333 (1985)

Matsuda, Ayako：“成人发病 1 型糖尿病的临床特征。”