Function, Regeneration, and Proliferation of Pancreatic β-Cells Centered on NAD

) concentration. Conversely, DNA damage to pancreatic β-cells activates poly (ADP-ribose) polymerase (PARP), promoting poly (ADP-ribosyl) ation. This depletes intracellular NAD, leading to pancreatic β-cell necrosis. Here, inhibiting PARP activity allows PARP to function as a transcription factor, enhancing the expression of the regeneration/proliferation factor RegI, leading to pancreatic β-cell regeneration and proliferation. Thus research findings from the Okamoto Laboratory suggest that in pancreatic β-cells, cell death, function, and regeneration/proliferation are closely interlinked, with NAD at the center. While NAD's role as a coenzyme is well-established, its physiological significance as a substrate for proteins such as sirtuins, CD38, and PARP, and its link to aging, have also been proposed. The Okamoto Laboratory's research on pancreatic β-cell function, death, and regeneration/proliferation centered on NAD represents pioneering work demonstrating NAD's critical importance in the living organism.