Abstract
We have proposed a unifying model for the action of alloxan and streptozotocin on pancreatic β-cells.1-5 Central to the model are breaks in the nuclear DNA of β-cells resulting from either an accumulation of oxygen radicals or alkylation of DNA. These breaks induce DNA repair involving the activation of poly(ADP-ribose) synthetase, which uses cellular NAD as a substrate; as a result, intra-cellular levels of NAD fall dramatically. The fall in cellular NAD inhibits the cellular activities including insulin synthesis, thus the β-cell ultimately dies.
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Unno, M. et al. (1992). Islet β-Cell Regeneration and Reg Genes. In: Vinik, A.I., Sirman, D.J. (eds) Pancreatic Islet Cell Regeneration and Growth. Advances in Experimental Medicine and Biology, vol 321. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3448-8_8
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DOI: https://doi.org/10.1007/978-1-4615-3448-8_8
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