Mechanisms of insulin resistance in the tumor-bearing state

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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.