Calcitonin gene-related peptide gene therapy suppresses reactive oxygen species in the pancreas and prevents mice from autoimmune diabetes.
Reactive oxygen species (ROS) is involved in autoimmune destruction of islet beta cells, which has been proven to be an important underlying pathogenesis for insulin dependent diabetes mellitus (IDDM). Calcitonin gene-related peptide (CGRP) is a widely distributed neuropeptide, which has been found to play an important role in protecting myocytes from ROS. We hypothesized that exogenous CGRP gene administration before the pathogenic stage of insulitis might suppress the production of ROS and provide a hopeful therapeutic intervention for autoimmune diabetes. We performed CGRP gene transfer by injecting naked plasmid directly into skeletal muscles of mice with electroporation enhancement to achieve a continuous expression of CGRP in skeletal muscles, and thereby its secretion into the circulation. The effect of CGRP gene transfer on the pathogenesis of diabetes was studied in autoimmune diabetic mice induced by multiple low dose streptozotocin (MLDS). The CGRP gene therapy decreased morbidity of autoimmune diabetes, and significantly ameliorated hyperglycemia in these mice. CGRP gene transfer inhibited the production of ROS and malondialdehyde (MDA). In addition, it enhanced the activity of catalase (CAT) and superoxide dismutase (SOD) significantly. The data suggest that intramuscular CGRP gene transfer ameliorates autoimmune destruction of islet beta cells, resulting in significant reduction in diabetes incidence of MLDS diabetes mice. CGRP benefits might be mediated at least in part by inhibiting the oxidative stress in islet beta cells of these mice.
She
Fei
F
Institute of Vascular Medicine, Third Hospital, Peking University, Beijing, 100083.
Sun
Wei
W
Mao
Jie-Ming
JM
Wang
Xian
X
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D007273:Injections, Intramuscular; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D015740:Calcitonin Gene-Related Peptide