Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10769268 | Biochemical and Biophysical Research Communications | 2005 | 7 Pages |
Abstract
This study investigated the role of endothelin-1 for hyperglycemia, vascular, and pancreatic injury in early type I diabetes in non-obese-diabetic (NOD) mice. Endothelium dependent relaxation to acetylcholine and vascular gene expression of endothelin converting enzyme (ECE) isoforms 1 and 2 were studied as indicators of vascular injury. Endothelial NO bioactivity in the aorta was reduced in diabetic NOD mice while vascular expression of ECE-1 and ECE-2 mRNA was increased compared with controls (all p < 0.05). Vascular histology was normal in all animals. Unexpectedly, treatment of prediabetic NOD mice for 6 weeks with the orally active ETA receptor antagonist BSF461314 prevented onset of diabetes without affecting insulitis severity. ETA receptor blockade also restored abnormal endothelial NO bioactivity and reduced ECE-1 and ECE-2 gene expression in NOD mice to levels comparable with healthy controls (p < 0.05). Moreover, secretion of endothelin-1 in a time-dependent fashion was observed by pancreatic islet β-cells cultured in vitro. These data suggest a critical role for ETA receptor signaling in the development of autoimmune forms of diabetes and the early vascular injury associated with it.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Jana Ortmann, Philipp C. Nett, Jennifer Celeiro, Tobias Traupe, Luigi Tornillo, Regina Hofmann-Lehmann, Elvira Haas, Beat Frank, Luigi M. Terraciano, Matthias Barton,