ArticleInternational journal of molecular medicine2013
High glucose activates the alternative ACE2/Ang-(1-7)/Mas and APN/Ang IV/IRAP RAS axes in pancreatic β-cells.
Article in International journal of molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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21 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Wharton's Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce SARS-CoV2-Induced Inflammatory Cytokines Under High Glucose and Uremic Toxin Conditions.Stem cells and development · 2021Pooled it
- Deep learning-driven proteomics analysis for gene annotation in the renin-angiotensin system.European journal of pharmacology · 2025Article
- Molecular dissection of the role of ACE2 in glucose homeostasis.Physiological reviews · 2025Review
- Hyperglycemia induced cathepsin L maturation linked to diabetic comorbidities and COVID-19 mortality.eLife · 2024Article
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection.Signal transduction and targeted therapy · 2024Article
- Mechanisms influencing the high prevalence of COVID-19 in diabetics: A systematic review.Medical research archives · 2023Article
- Can Probiotics, ParticularlyBiology · 2023Review
- A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.Cell metabolism · 2022Article
- ACE2 function in the pancreatic islet: Implications for relationship between SARS-CoV-2 and diabetes.Acta physiologica (Oxford, England) · 2021Review
- A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19.Frontiers in public health · 2021Article
- Angiotensin-converting enzyme 2 influences pancreatic and renal function in diabetic mice.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Potentially modifiable factors to reduce severity of COVID-19 in type 2 diabetes.Nutrition & diabetes · 2020Article
- Prevention and Management of Type 2 Diabetes and Metabolic Syndrome in the Time of COVID-19: Should We Add a Cup of Coffee?Frontiers in nutrition · 2020Review
- Positive association between KCNJ5 rs2604204 (A/C) polymorphism and plasma aldosterone levels, but also plasma renin and angiotensin I and II levels, in newly diagnosed hypertensive Chinese: a case-control study.Journal of human hypertension · 2017Article
- High-fat diet-induced glucose dysregulation is independent of changes in islet ACE2 in mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment.Frontiers in behavioral neuroscience · 2016Article
- ACE2 deficiency reduces β-cell mass and impairs β-cell proliferation in obese C57BL/6 mice.American journal of physiology. Endocrinology and metabolism · 2015Article
- Angiotensin AT2 receptor agonist prevents salt-sensitive hypertension in obese Zucker rats.American journal of physiology. Renal physiology · 2015Article
- Persistent hyperglycemia modulates gut immune function and microbiota in rats.Journal of intensive care · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation of the classical angiotensin (Ang)-converting enzyme (ACE)/Ang II/Ang II type 1 receptor (AT1R) axis of the renin-angiotensin system (RAS) has been associated with islet dysfunction and insulin resistance. Hyperglycaemia, hypertension and obesity, major components of metabolic syndrome, are all associated with increased systemic and tissue levels of Ang II. Whereas it is well established that Ang II, by binding to AT1R, impairs glucose-stimulated insulin secretion and insulin signaling, the contribution of alternative RAS axes to β-cell function remains to be fully elucidated. In this study, using the BRIN-BD11 rat insulinoma cell line, we i) examined the basal expression levels of components of classical and alternative RAS axes and ii) investigated the effects of normal (5.5 mM) and elevated (11, 15, 25 mM) glucose concentrations on their expression and/or enzymatic activity by means of reverse transcription quantitative PCR (RT-qPCR), immunoblot analysis and enzymatic activity assays. The results correlated with the insulin production and release. Essential components of all RAS axes were found to be expressed in the BRIN-BD11 cells. Components of the alternative RAS axes, ACE2, neutral endopeptidase 24.11, Mas receptor (Mas), aminopeptidases A (APA) and N (APN) and insulin-regulated aminopeptidase (IRAP) showed an increased expression/activity in response to high glucose. These alterations were paralleled by the glucose-dependent increase in insulin production and release. By contrast, components of the classical RAS axis, ACE, AT1R and Ang II type 2 receptor (AT2R), remained largely unaffected under these conditions. Glucose induced the activation of the alternative ACE2/Ang-(1-7)/Mas and APN/Ang IV/IRAP RAS axes simultaneously with the stimulation of insulin production/release. Our data suggest the existence of a functional link between the local RAS axis and pancreatic β-cell function; however, further studies are required to confirm this hypothesis.
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