It is reasonable to assume that poly(ADP-ribose) synthetase inhibitors induce pancreatic B-cell regeneration, thereby improving diabetes mellitus caused by partial pancreatectomy. The fact that poly(ADP-ribose) synthetase inhibitors induce pancreatic B-cell regeneration seems to mean that the enzyme may play a role in restricting B-cell replication. This concept may be reconcilable with the observations that poly(ADP-ribosyl)ation suppresses DNA replication in rat liver nuclei and that nicotinamide stimulates DNA synthesis in HeLa cells. In the first part of this paper it was shown that alloxan and streptozotocin induce islet DNA strand breaks and that poly(ADP-ribose) synthetase acts to repair the DNA breaks, consuming islet NAD. The rapid and marked depletion of islet NAD has been regarded as the primary molecular mechanism behind the destruction of the B-cells. Therefore, poly(ADP-ribose) synthetase inhibitors can prophylactically prevent alloxan and streptozotocin diabetes by blocking the NAD consumption. Evidence in the second part of the paper suggested an alternative function of poly(ADP-ribose) synthetase inhibitors in the improvement of surgical diabetes. In this case, poly(ADP-ribose) synthetase inhibitors may relieve restriction of DNA replication and so cause B-cell regeneration. Since a low capacity for B-cell regeneration has been suggested as a predisposition for the development of human diabetes, the present study may provide a novel clue for the prevention and treatment of human diabetes.
|Number of pages||6|
|Journal||Biomedica Biochimica Acta|
|Publication status||Published - 1985 Jan 1|
ASJC Scopus subject areas