| http://purl.uniprot.org/citations/28559246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28559246 | http://www.w3.org/2000/01/rdf-schema#comment | "Recent work has renewed interest in therapies targeting the renin-angiotensin system (RAS) to improve β-cell function in type 2 diabetes. Studies show that generation of angiotensin-(1-7) by ACE2 and its binding to the Mas receptor (MasR) improves glucose homeostasis, partly by enhancing glucose-stimulated insulin secretion (GSIS). Thus, islet ACE2 upregulation is viewed as a desirable therapeutic goal. Here, we show that, although endogenous islet ACE2 expression is sparse, its inhibition abrogates angiotensin-(1-7)-mediated GSIS. However, a more widely expressed islet peptidase, neprilysin, degrades angiotensin-(1-7) into several peptides. In neprilysin-deficient mouse islets, angiotensin-(1-7) and neprilysin-derived degradation products angiotensin-(1-4), angiotensin-(5-7), and angiotensin-(3-4) failed to enhance GSIS. Conversely, angiotensin-(1-2) enhanced GSIS in both neprilysin-deficient and wild-type islets. Rather than mediating this effect via activation of the G-protein-coupled receptor (GPCR) MasR, angiotensin-(1-2) was found to signal via another GPCR, namely GPCR family C group 6 member A (GPRC6A). In conclusion, in islets, intact angiotensin-(1-7) is not the primary mediator of beneficial effects ascribed to the ACE2/angiotensin-(1-7)/MasR axis. Our findings warrant caution for the concurrent use of angiotensin-(1-7) compounds and neprilysin inhibitors as therapies for diabetes."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.org/dc/terms/identifier | "doi:10.2337/db16-1318"xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/author | "Watson M."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/author | "Raleigh D.P."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/author | "Griesbach R."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/author | "Brar G.S."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/author | "Ruzsicska B."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/author | "Zraika S."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/author | "Welch A."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/author | "Barrow B.M."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/author | "Choung E."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/name | "Diabetes"xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/pages | "2201-2212"xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/title | "Neprilysin Is Required for Angiotensin-(1-7)'s Ability to Enhance Insulin Secretion via Its Proteolytic Activity to Generate Angiotensin-(1-2)."xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://purl.uniprot.org/core/volume | "66"xsd:string |
| http://purl.uniprot.org/citations/28559246 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28559246 |
| http://purl.uniprot.org/citations/28559246 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28559246 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YW93-mappedCitation-28559246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28559246 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YWA6-mappedCitation-28559246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28559246 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YWB9-mappedCitation-28559246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28559246 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YY36-mappedCitation-28559246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28559246 |
| http://purl.uniprot.org/uniprot/#_Q61391-mappedCitation-28559246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28559246 |
| http://purl.uniprot.org/uniprot/#_Q8BNU9-mappedCitation-28559246 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28559246 |