Protection by picolinamide, a novel inhibitor of poly (ADP-ribose) synthetase, against both streptozotocin-induced depression of proinsulin synthesis and reduction of NAD content in pancreatic islets

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Abstract

Picolinamide, 2-pyridinecarboxylic acid amide, was found to be a strong inhibitor of poly (ADP-ribose) synthetase of nuclei from rat pancreatic islet cells. Another experiment using isolated pancreatic islets of rats showed that picolinamide protects against streptozotocin-induced depression of proinsulin synthesis as well as against streptozotocin-induced reduction of NAD content. The protection by picolinamide against the NAD depression was considered to be due to the blockage of an increased degradation of NAD mediated by a streptozotocin-induced increase in poly (ADP-ribose) synthetase activity. A possible mechanism of streptozotocin diabetes and its prevention is discussed.

References (37)

  • I.M. Murray-Lyon et al.

    Lancet

    (1968)
  • M. Hinz et al.

    FEBS Lett

    (1973)
  • J. Preiss et al.

    J. Biol. Chem

    (1957)
  • Y. Nishizuka et al.

    J. Biol. Chem

    (1963)
  • L.S. Dietrich et al.

    J. Biol. Chem

    (1966)
  • W.J.D. Whish et al.

    Biochem. Biophys. Res. Commun

    (1975)
  • T. Sugimura

    Prog. Nucleic Acid Res. Mol. Biol

    (1973)
  • Y. Tanigawa et al.

    Biochem. Biophys. Res. Commun

    (1977)
  • J.M. Kissane et al.

    J. Biol. Chem

    (1958)
  • H. Okamoto et al.

    Biochem. Biophys. Res. Commun

    (1973)
  • N. Itoh et al.

    FEBS Lett

    (1977)
  • J. Preiss et al.

    FEBS Lett

    (1971)
  • L. Burzio et al.

    Biochem. Biophys. Res. Commun

    (1970)
  • M. Miwa et al.

    Arch. Biochem. Biophys

    (1977)
  • N. Rakieten et al.

    Cancer Chemother. Rep

    (1963)
  • P.S. Schein et al.

    Cancer Res

    (1967)
  • R.M. Pitkin et al.

    Diabetes

    (1970)
  • A. Maldonato et al.

    Diabetologia

    (1976)
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    This work has been supported in part by Grants-in-Aid for Cancer Research and for Scientific Research from the Ministry of Education, Science and Culture, Japan.

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