Wednesday, November 2, 2016

Insulin enhances the transmembrane transport of drugs. Experiments with MCF-7 human breast cancer cells in vitro have shown a 10,000-fold increase in the cytotoxic effect of methotrexate with insulin, and an in vivo experiment with rats has demonstrated an insulin-induced increase in passage through the blood-brain barrier of zidovudine (AZ’!).

Insulin enhances the transmembrane transport of drugs. Experiments with MCF-7 human breast cancer cells in vitro have shown a 10,000-fold increase in the cytotoxic effect of methotrexate with insulin, and an in vivo experiment with rats has demonstrated an insulin-induced increase in passage through the blood-brain barrier of zidovudine (AZ’!).
These effects may be mediated through insulin receptors, possibly via coupling with the process of receptor-mediated endocytosis. Cell membrane-derived second messengers of insulin may also play a role in altering the mechanics of membrane transport.
Metabolic modification of cancer cell metabolism by insulin could account for some of the observed potentiation of drug effect Insulin stimulates DNA and RNA synthesis through direct interaction with its receptors on nuclear membranes, and it may produce a similar effect via cross-reaction with IGF1 receptors. Such actions would serve to augment anticancer drug cytotoxicity, particularly for the cell cycle-specific agents (methotrexate, 5-fluorouracil).

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