Abstract
Ionizing radiation evokes biological responses against oxidative stress as well as those against DNA break and oncogenesis, through the interaction with intracellular molecules. Because the stress responses are regulated by the system involved in metabolic homeostasis, it is possible that ionizing radiation can be used for the therapy of human metabolic syndrome. We have found that continuous gamma-irradiation at low dose rate ameliorates type II diabetes in db/db mice genetically lacking leptin receptors, and elongates their life span. Here we studied mechanism of the amelioration of Type II diabetes by low dose rate gamma-irradiation. Eleven-wk female db/db mice were continuously irradiated at 174 microGy/h for 2-3 weeks in the irradiation room bearing 1.8PBq cobalt-60 as a radiation source, and found that the treatment significantly improved diabetes in glucose tolerance test. Reduction of blood insulin and degeneration of pancreatic islets, characteristics in chronic phase of type II diabetes, were significantly suppressed by continuous low dose rate irradiation, suggesting that it protects pancreatic islets from glucose toxicity. The irradiation suppressed apoptosis in pancreatic islets. Enhancement of SOD-2 expression was demonstrated by immunohistochemisty and RT-PCR in pancreas. These results suggest that continuous low dose rate gamma-irradiation ameliorates type II diabetes through the transcription activation of host surveillance system against oxidative stress.
