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Streptozotocin and alloxan induce DNA strand breaks and poly(ADP–ribose) synthetase in pancreatic islets

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Abstract

Streptozotocin, which produces diabetes mellitus in experimental animals1–3, has been reported to reduce the level of NAD in pancreatic islets4,5 and to inhibit islet synthesis of proinsulin6. The decrease in NAD is due to increased NAD degradation mediated by islet nuclear poly(ADP–ribose) synthetase7,8. Evidence suggests that poly(ADP–ribose) synthetase is activated when DNA is fragmented9–17. Here we describe that both Streptozotocin and alloxan, which also produces experimental diabetes mellitus1,2, cause DNA strand breaks which stimulate nuclear poly(ADP–ribose) synthetase, thereby depleting intracellular NAD and inhibiting proinsulin synthesis in isolated pancreatic islets of rats.

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Authors and Affiliations

  1. Department of Biochemistry, Toyama Medical and Pharmaceutical University, School of Medicine, Toyama, 930-01, Japan

    Hiroshi Yamamoto, Yasuko Uchigata & Hiroshi Okamoto

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  1. Hiroshi Yamamoto
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  2. Yasuko Uchigata
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  3. Hiroshi Okamoto
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Yamamoto, H., Uchigata, Y. & Okamoto, H. Streptozotocin and alloxan induce DNA strand breaks and poly(ADP–ribose) synthetase in pancreatic islets. Nature 294, 284–286 (1981). https://doi.org/10.1038/294284a0

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