Mechanism of Insulin Resistance in Insulin Receptor Disease.

胰岛素受体疾病中胰岛素抵抗的机制。

• 批准号: 59480253
• 负责人: KOBAYASHI Masashi
• 金额: $ 3.9万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1984
• 资助国家: 日本
• 起止时间: 1984 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-59480253/
• 关键词: Insulin receptor; Insulin resistance; Kinase activity of beta-subunit; IGF-1; インスリン作用

We investigated the mechanism of insulin resistance of insulin receptor diseases, Type A,B and C. For Type A, five families were examined and the binding studies of transformed lymphocytes, erythrocytes as well as fibrobalsts from these patients revealed decreased insulin receptor numbers. Decreased kinase activity of beta-subunits were proportional tothe extent of decreased binding. As for Type C, receptor binding and kinase activity of transformed lymphocytes were normal, indicating that the defect was at post-kinase sites.In Type B, anti-insulin receptor antibody demonstrated various insulin like activity depend on the cell types such as glucose uptake or kunase activity. Thus, antibody's recognition was various depend on the cell types.Further studies are necessary to elucidate the mechanism of decreased receptor number in Type A and to identify the exact site of insulin resistance in Type C, possibly glucose transporter. To clarify these unkown probelms, gene analysis of insulin receptor and glucose transporter is mandatory.

本文对A、B、C型胰岛素受体疾病的胰岛素抵抗机制进行了探讨。对于A型，检查了五个家族，并且来自这些患者的转化淋巴细胞、红细胞以及成纤维细胞的结合研究显示胰岛素受体数目减少。β-亚基激酶活性的降低与结合降低的程度成正比。C型转化淋巴细胞的受体结合和激酶活性正常，表明其缺陷位于激酶后位点，而B型转化淋巴细胞的胰岛素样活性与细胞类型有关，如葡萄糖摄取或kunase活性。因此，抗体的识别因细胞类型不同而不同，需要进一步研究以阐明A型受体数量减少的机制，并确定C型胰岛素抵抗的确切部位，可能是葡萄糖转运蛋白。为了阐明这些未知的问题，胰岛素受体和葡萄糖转运蛋白的基因分析是必不可少的。

项目成果

Takata, Y.: "A primary defect in insulin receptor in a young male patient with insulin resistance." Metabolism. 35. 950-955 (1986)

Takata, Y.：“患有胰岛素抵抗的年轻男性患者胰岛素受体的主要缺陷。”

Maegawa, H.: "Effect of diet change on insulin action:difference between muscles and adipocytes." Am J Physiol. 251. E616-E623 (1986)

Maekawa, H.：“饮食变化对胰岛素作用的影响：肌肉和脂肪细胞之间的差异。”

Kobayashi,M.: In.Symposium on Insulin Treatment. in press.

Kobayashi,M.：In.胰岛素治疗研讨会。

小林正: "レセプターと疾患" 中山書店, 362 (1986)

小林正：《受体与疾病》中山书店，362 (1986)

Maegawa,H.: Am J Physiol. 251. E616-E623 (1986)

前川，H.：《美国生理学杂志》。