Mechanisms of insulin resistance in the tumor-bearing state

荷瘤状态下胰岛素抵抗的机制

• 批准号: 05454360
• 负责人: MATSUMOTO Akihiko
• 金额: $ 4.42万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454360/
• 关键词: insulin resistance; glucose transporter; glucose clamp; 癌悪液質; インスリンレジスタンス; グリコーストランスポーター; euglycemic clamp

This study was conducted to elucidate the mechanisms of insulin resistance, observed in the tumor-bearing hosts by investigating insulin-dependent glucose transporter. Specific questions raised were 1. to elucidate insulin resistance in cancer patients and 2. clarify the role of glucose transporters in inducing cancer cachexia.Results1. We have examined 50 cases of cancer patients by englycemic hyperinsulinemic glucose clamp technique and insulin resistance was documented in most of those cases. This was not related with either stage of the disease nor degree of weight loss but was tumor-depended changes.2. In Fisher rat with MCA sarcoma, glucose transport activity was significantly decreased in tumor-bearing rats compared with pair-fed control. Decrease in GLUT4 was due to decreased intracytoplasmic pool of this protein and decreased translocation to the membrane.3. GLUT4 was demonstrated in 25% of human cancer specimens. This was not related with degree of peripheral insulin resistance. Forced administration of insulin and nutrients in those patients may facilitate tumor growth without helping nutrition of the host.

本研究旨在通过研究胰岛素依赖性葡萄糖转运体来阐明在荷瘤宿主中观察到的胰岛素抵抗机制。提出的具体问题有：1。目的：探讨胰岛素抵抗在肿瘤患者中的作用。阐明葡萄糖转运体在诱导癌症恶病质中的作用。我们对50例癌症患者进行了高血糖-高胰岛素-葡萄糖钳夹技术检查，大多数病例均出现胰岛素抵抗。这与疾病的分期和体重减轻的程度无关，而是与肿瘤相关的变化。在MCA肉瘤Fisher大鼠中，荷瘤大鼠的葡萄糖转运活性与配对喂养对照组相比显著降低。GLUT4的减少是由于该蛋白的胞浆内池减少和向膜的易位减少。在25%的人类癌症标本中发现了GLUT4。这与外周胰岛素抵抗的程度无关。在这些患者中，强行使用胰岛素和营养物可能会促进肿瘤的生长，而对宿主的营养没有帮助。

项目成果

Noguchi Y: "The effect of prolouged hyperglycemia on metabolic alterations in the subtotally pancneatectomized rat" Surg Today. 24. 987-993 (1994)

Noguchi Y：“长期高血糖对胰腺次全切除大鼠代谢变化的影响”《今日外科》。

Makino T: "Ultrastructural alterations of hepatocyte in the tumor-bearing,cachectic rat" Int J Exp Path. 75. 433-440 (1994)

Makino T：“荷瘤恶病质大鼠肝细胞的超微结构改变”Int J Exp Path。

野口芳一: "分子生物学レベルから見た担癌時に煮起させる代謝異常" Medical postgraduates. 31. 74-80 (1993)

Yoshikazu Noguchi：“从分子生物学水平来看癌症发生过程中发生的代谢异常”医学研究生 31. 74-80 (1993)。

Yoshikawa T: "Effects of tumor removal and body weight loss on insulin resistance in cancer paticnts" Surgery. 116. 62-66 (1994)

Yoshikawa T：“肿瘤切除和体重减轻对癌症患者胰岛素抵抗的影响”手术。

Yoshikawa T.: "Effects of tumor removal and body weight loss on insulin resistance in cancer patients" Surgery. Volume 116. 62-66 (1994)

Yoshikawa T.：“肿瘤切除和体重减轻对癌症患者胰岛素抵抗的影响”手术。