期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 478, 期 2, 页码 136-142出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2008.08.001
关键词
glucagon-like peptide-1 (GLP-1); exendin; incretin; hormone; non-peptide agonist; vasorelaxation; aorta
资金
- Physiological Society and the School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast
- Diabetes UK
- Medical Research Council [G0601215] Funding Source: researchfish
- MRC [G0601215] Funding Source: UKRI
increasing evidence from both clinical and experimental studies indicates that the insulin-releasing hormone, glucagon-like peptide-1 (GLP-1) may exert additional protective/reparative effects on the cardiovascular system. The aim of this study was to examine vasorelaxant effects of GLP-1(7-36)amide, three structurally-related peptides and a non-peptide GLP-1 agonist in rat aorta. Interestingly, all GLP-1 compounds, including the established GLP-1 receptor antagonist, exendin (9-39) caused concentration-dependent relaxation. Mechanistic studies employing hyperpolarising concentrations of potassium or glybenclamide revealed that these relaxant effects are mediated via specific activation of ATP-sensitive potassium channels. Further experiments using a specific membrane-permeable cyclic AMP (cAMP) antagonist, and demonstration of increased cAMP production in response to GLP-1 illustrated the critical importance of this pathway. These data significantly extend previous observations suggesting that GLP-1 may modulate vascular function, and indicate that this effect may be mediated by the GLP-1 receptor. However, further studies are required in order to establish whether GLP-1 related agents may confer additional cardiovascular benefits to diabetic patients. (c) 2008 Elsevier Inc. All rights reserved.
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