Abstract
High doses of ionizing radiation (HDIR) are known to induce cellular damage, whereas low-dose ionizing radiation (LDIR) may trigger protective biological responses. Recent studies have explored the potential benefits of LDIR in treating diabetes and its complications. However, the direct effects of LDIR on pancreatic β-cells and the underlying mechanisms remain to be elucidated. This study aimed to evaluate the effects of LDIR on pancreatic β-cell functionality and elucidate the underlying molecular mechanisms involved. Rat RIN-m5F cells were exposed to LDIR (25 mGy) or HDIR (2.5 Gy) to examine changes in insulin mRNA expression, secretion, DNA damage, and apoptosis. The roles of reactive oxygen species (ROS) and the p38 mitogen-activated protein kinase (MAPK) pathway were assessed via the use of antioxidants and pathway inhibitors. The findings indicated that LDIR transiently increased both insulin synthesis and secretion without inducing apoptosis or affecting cell proliferation. In contrast, HDIR induced a significant increase in apoptosis and a marked inhibition of proliferation. LDIR was observed to temporarily increase ROS production, activating the p38 MAPK pathway and facilitating insulin synthesis via the upregulation of PDX-1. Notably, LDIR did not induce DNA double-strand breaks or activate the ATM-dependent DNA repair pathways, unlike HDIR, which induced apoptosis through overactivation of the ROS/p38 MAPK pathway. In conclusion, LDIR enhanced pancreatic β-cell functionality via ROS-mediated activation of the p38 MAPK pathway, highlighting its potential therapeutic applications in diabetes management.