ArticleAmerican journal of physiology. Renal physiology2014
Insulin treatment attenuates renal ADAM17 and ACE2 shedding in diabetic Akita mice.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Currently prescribed drugs in the UK that could upregulate or downregulate ACE2 in COVID-19 disease: a systematic review.BMJ open · 2020Pooled it
- METTL3 mediates mJournal of advanced research · 2026Article
- Hyperglycemia-Induced Endothelial Dysfunction: From Classical Pathogenetic Mechanisms to Emerging Insights into ACE2 Protective Action.International journal of molecular sciences · 2026Review
- Molecular dissection of the role of ACE2 in glucose homeostasis.Physiological reviews · 2025Review
- Herbal Medicines as Complementary Therapy for Managing Complications in COVID-19 Patients with Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Insulin restores renal neprilysin (NEP) and attenuates the shedding of urinary NEP and KIM-1 in diabetic Akita mice.Frontiers in pharmacology · 2025Article
- Mesenchymal stem cell-derived extracellular vesicles ameliorate renal interstitial fibrosis via the miR-13474/ADAM17 axis.Scientific reports · 2024Article
- Bibliometric and visual analysis of ACE2/Ang 1-7/MasR axis in diabetes and its microvascular complications from 2000 to 2023.Heliyon · 2024Article
- Sirt1 activation prevents high glucose-induced angiotensin converting enzyme 2 downregulation in renal tubular cells by regulating the TIMP3/ADAM17 pathway.Molecular biology reports · 2024Article
- Potential Drugs in COVID-19 Management.Current medicinal chemistry · 2024Review
- Mechanisms influencing the high prevalence of COVID-19 in diabetics: A systematic review.Medical research archives · 2023Article
- ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification.Journal of biomedical science · 2023Review
- New-onset diabetes in COVID-19: The molecular pathogenesis.BioMedicine · 2023Review
- Effects of Metformin, Insulin on Hematological Parameters of COVID-19 Patients with Type 2 Diabetes.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2022Article
- Guidelines on models of diabetic heart disease.American journal of physiology. Heart and circulatory physiology · 2022Review
- Mechanisms contributing to adverse outcomes of COVID-19 in obesity.Molecular and cellular biochemistry · 2022Review
- Review
- COVID-19, liver dysfunction and pathophysiology: A conceptual discussion.World journal of gastroenterology · 2022Article
- The ACE2 Receptor for Coronavirus Entry Is Localized at Apical Cell-Cell Junctions of Epithelial Cells.Cells · 2022Article
- Association of Maternal Diabetes and Autism Spectrum Disorders in Offspring: a Study in a Rodent Model of Autism.Journal of molecular neuroscience : MN · 2022Article
13 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
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Abstract
Angiotensin-converting enzyme 2 (ACE2) is located in several tissues and is highly expressed in renal proximal tubules, where it degrades the vasoconstrictor angiotensin II (ANG II) to ANG-(1-7). Accumulating evidence supports protective roles of ACE2 in several disease states, including diabetic nephropathy. A disintegrin and metalloprotease (ADAM) 17 is involved in the shedding of several transmembrane proteins, including ACE2. Our previous studies showed increased renal ACE2, ADAM17 expression, and urinary ACE2 in type 2 diabetic mice (Chodavarapu H, Grobe N, Somineni HK, Salem ES, Madhu M, Elased KM. PLoS One 8: e62833, 2013). The aim of the present study was to determine the effect of insulin on ACE2 shedding and ADAM17 in type 1 diabetic Akita mice. Results demonstrate increased renal ACE2 and ADAM17 expression and increased urinary ACE2 fragments (≈70 kDa) and albumin excretion in diabetic Akita mice. Immunostaining revealed colocalization of ACE2 with ADAM17 in renal tubules. Renal proximal tubular cells treated with ADAM17 inhibitor showed reduced ACE2 shedding into the media, confirming ADAM17-mediated shedding of ACE2. Treatment of Akita mice with insulin implants for 20 wk normalized hyperglycemia and decreased urinary ACE2 and albumin excretion. Insulin also normalized renal ACE2 and ADAM17 but had no effect on tissue inhibitor of metalloproteinase 3 (TIMP3) protein expression. There was a positive linear correlation between urinary ACE2 and albuminuria, blood glucose, plasma creatinine, glucagon, and triglycerides. This is the first report showing an association between hyperglycemia, cardiovascular risk factors, and increased shedding of urinary ACE2 in diabetic Akita mice. Urinary ACE2 could be used as a biomarker for diabetic nephropathy and as an index of intrarenal ACE2 status.
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