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GLP-1 Receptor Expression Within the Human Heart

Baggio, Laurie L ; Yusta, Bernardo ; Mulvihill, Erin E ; Cao, Xiemin ; Streutker, Catherine J ; Butany, Jagdish ; Cappola, Thomas P ; Margulies, Kenneth B ; Drucker, Daniel J

Endocrinology (Philadelphia), 2018-04, Vol.159 (4), p.1570-1584 [Periódico revisado por pares]

Washington, DC: Endocrine Society

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GLP-1 Receptor Expression Within the Human Heart
Autor: Baggio, Laurie L ; Yusta, Bernardo ; Mulvihill, Erin E ; Cao, Xiemin ; Streutker, Catherine J ; Butany, Jagdish ; Cappola, Thomas P ; Margulies, Kenneth B ; Drucker, Daniel J
Assuntos: Animals ; Antisera ; Blood vessels ; Cardiac ventricles ; Cardiomyocytes ; Cell Line ; Coronary artery ; Cricetinae ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Endocrinology ; Female ; Fibroblasts ; Fibroblasts - metabolism ; Gene expression ; Glands ; Glucagon-Like Peptide-1 Receptor - genetics ; Glucagon-Like Peptide-1 Receptor - metabolism ; Glucagon-Like Peptide-2 Receptor - genetics ; Glucagon-Like Peptide-2 Receptor - metabolism ; Heart ; Humans ; Hybridization ; Islets of Langerhans - metabolism ; Localization ; Muscle, Smooth, Vascular - metabolism ; Muscles ; Myocardial infarction ; Myocardium - metabolism ; Myocytes, Smooth Muscle - metabolism ; Pancreas ; Polymerase chain reaction ; Proteins ; Reverse transcription ; Smooth muscle ; Ventricle ; Western blotting
É parte de: Endocrinology (Philadelphia), 2018-04, Vol.159 (4), p.1570-1584
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Descrição: Abstract Glucagonlike peptide-1 receptor (GLP-1R) agonists, which are used to treat type 2 diabetes and obesity, reduce the rates of myocardial infarction and cardiovascular death. GLP-1R has been localized to the human sinoatrial node; however, its expression in ventricular tissue remains uncertain. Here we studied GLP-1R expression in the human heart using GLP-1R–directed antisera, quantitative polymerase chain reaction (PCR), reverse transcription PCR to detect full-length messenger RNA (mRNA) transcripts, and in situ hybridization (ISH). GLP1R mRNA transcripts, encompassing the entire open reading frame, were detected in all four cardiac chambers from 15 hearts at levels approximating those detected in human pancreas. In contrast, cardiac GLP2R expression was relatively lower, and cardiac GCGR expression was sporadic and not detected in the left ventricle. GLP1R mRNA transcripts were not detected in RNA from human cardiac fibroblasts, coronary artery endothelial, or vascular smooth muscle cells. Human Brunner glands and pancreatic islets exhibited GLP-1R immunopositivity and abundant expression of GLP1R mRNA transcripts by ISH. GLP1R transcripts were also detected by ISH in human cardiac sinoatrial node tissue. However, definitive cellular localization of GLP1R mRNA transcripts or immunoreactive GLP-1R protein within human cardiomyocytes or cardiac blood vessels remained elusive. Moreover, validated GLP-1R antisera lacked sufficient sensitivity to detect expression of the endogenous islet or cardiac GLP-1R by Western blotting. Hence, although human cardiac ventricles express the GLP1R, the identity of one or more ventricular cell type(s) that express a translated GLP1R protein requires further clarification with highly sensitive methods of detection. We assess current methods of detecting GLP-1R expression and apply different techniques in the investigation of GLP-1R expression within distinct chambers and cell types in the human heart.
Editor: Washington, DC: Endocrine Society
Idioma: Inglês

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GLP-1 Receptor Expression Within the Human Heart

Baggio, Laurie L ; Yusta, Bernardo ; Mulvihill, Erin E ; Cao, Xiemin ; Streutker, Catherine J ; Butany, Jagdish ; Cappola, Thomas P ; Margulies, Kenneth B ; Drucker, Daniel J

Washington, DC: Endocrine Society

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