Okamoto model for necrosis and its expansions, CD38-cyclic ADP-ribose signal system for intracellular Ca²⁺ mobilization and Reg (Regenerating gene protein)-Reg receptor system for cell regeneration.

ABSTRACT: In pancreatic islet cell culture models and animal models, we studied the molecular mechanisms involved in the development of insulin-dependent diabetes. The diabetogenic agents, alloxan and streptozotocin, caused DNA strand breaks, which in turn activated poly(ADP-ribose) polymerase/synthetase (PARP) to deplete NAD⁺, thereby inhibiting islet β-cell functions such as proinsulin synthesis and ultimately leading to β-cell necrosis. Radical scavengers protected against the formation of DNA strand breaks and inhibition of proinsulin synthesis. Inhibitors of PARP prevented the NAD⁺ depletion, inhibition of proinsulin synthesis and β-cell death. These findings led to the proposed unifying concept for β-cell damage and its prevention (the Okamoto model). The model met one pr

SUBMITTER: Okamoto H 

PROVIDER: S-EPMC8553518 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature