ArticleDiabetes2017
Neprilysin Is Required for Angiotensin-(1-7)'s Ability to Enhance Insulin Secretion via Its Proteolytic Activity to Generate Angiotensin-(1-2).
Article in Diabetes, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- A physiology-based mathematical model of the renin-angiotensin system, bone remodeling, and calcium homeostasis: Effects of estrogen and renin-angiotensin system inhibitors.PLoS computational biology · 2026Article
- Hypertonicity during a rapid rise in D-glucose mediates first-phase insulin secretion.Frontiers in endocrinology · 2024Article
- Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena.Journal of diabetes · 2023Review
- Effectiveness of Hydroalcoholic Seed Extract ofOxidative medicine and cellular longevity · 2023Article
- Going viral in the islet: mediators of SARS-CoV-2 entry beyond ACE2.Journal of molecular endocrinology · 2022Review
- Adipose Tissue Secretion Pattern Influences β-Cell Wellness in the Transition from Obesity to Type 2 Diabetes.International journal of molecular sciences · 2022Review
- Insulinotropic Effects of Neprilysin and/or Angiotensin Receptor Inhibition in Mice.Frontiers in endocrinology · 2022Article
- ACE2 function in the pancreatic islet: Implications for relationship between SARS-CoV-2 and diabetes.Acta physiologica (Oxford, England) · 2021Review
- Expression of SARS-CoV-2 receptor "ACE2" in human pancreatic β cells: to be or not to be!Islets · 2021Review
- Review
- Molecular Mechanisms Involved in Intrarenal Renin-Angiotensin and Alternative Pathways in Diabetic Nephropathy - A Review.The review of diabetic studies : RDS · 2021Review
- ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19.Clinical science (London, England : 1979) · 2020Review
- Neprilysin Inhibitors and Angiotensin(1-7) in COVID-19.The British journal of cardiology · 2020Article
- Endocrine Significance of SARS-CoV-2's Reliance on ACE2.Endocrinology · 2020Review
- Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost.Biochemical pharmacology · 2020Review
- Article
- Peptidomic Analysis of Urine from Youths with Early Type 1 Diabetes Reveals Novel Bioactivity of Uromodulin PeptidesMolecular & cellular proteomics : MCP · 2020Article
- Potential mechanisms of beneficial effect of sacubitril/valsartan on glycemic control.Therapeutic advances in endocrinology and metabolism · 2020Review
- Neprilysin inhibition: a new therapeutic option for type 2 diabetes?Diabetologia · 2019Review
- Cardiovascular effects of small peptides of the renin angiotensin system.Physiological reports · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.