ArticleEndocrinology2008
Renin inhibition attenuates insulin resistance, oxidative stress, and pancreatic remodeling in the transgenic Ren2 rat.
Article in Endocrinology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 74 citations in OpenAlex.
- Angiotensin receptor blocker/diuretic combination preserves insulin responses in obese hypertensives.Journal of hypertension · 2010Trial
- Pseudocannabinoid H4CBD improves glucose response during advanced metabolic syndrome in OLETF rats independent of increase in insulin signaling proteins.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- Article
- Epigenetic modifications of the renin-angiotensin system in cardiometabolic diseases.Clinical science (London, England : 1979) · 2021Review
- Screening and Identification of Key Genes for Activation of Islet Stellate Cell.Frontiers in endocrinology · 2021Article
- Review
- Decades-old renin inhibitors are still struggling to find a niche in antihypertensive therapy. A fleeting look at the old and the promising new molecules.Bioorganic & medicinal chemistry · 2020Review
- Sex differences in the metabolic effects of the renin-angiotensin system.Biology of sex differences · 2019Review
- Chronic AT1 blockade improves glucose homeostasis in obese OLETF rats.The Journal of endocrinology · 2018Article
- Exogenous thyroxine improves glucose intolerance in insulin-resistant rats.The Journal of endocrinology · 2017Article
- Article
- Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced diabetic nephropathy in female rats.Naunyn-Schmiedeberg's archives of pharmacology · 2016Article
- Cardiometabolic crosstalk in obesity-associated arterial hypertension.Reviews in endocrine & metabolic disorders · 2016Review
- Aliskiren Reduces Hepatic steatosis and Epididymal Fat Mass and Increases Skeletal Muscle Insulin Sensitivity in High-Fat Diet-Fed Mice.Scientific reports · 2016Article
- Metabolic impact of adding a thiazide diuretic to captopril.Hypertension (Dallas, Tex. : 1979) · 2013Article
- Direct renin inhibition modulates insulin resistance in caveolin-1-deficient mice.Metabolism: clinical and experimental · 2013Article
- Aliskiren attenuates steatohepatitis and increases turnover of hepatic fat in mice fed with a methionine and choline deficient diet.PloS one · 2013Article
- Angiotensin receptor blockade recovers hepatic UCP2 expression and aconitase and SDH activities and ameliorates hepatic oxidative damage in insulin resistant rats.Endocrinology · 2012Article
- Oxidative stress in the cardiorenal metabolic syndrome.Current hypertension reports · 2012Review
- Oral renin inhibitors in clinical practice: a perspective review.Therapeutic advances in chronic disease · 2012Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Emerging evidence indicates that pancreatic tissue expresses all components of the renin-angiotensin system. However, the functional role is not well understood. This investigation examined renin inhibition on pancreas structure/function in the transgenic Ren2 rat harboring the mouse renin gene, a model of tissue renin overexpression. Renin is the rate-limiting step in the generation of angiotensin II (Ang II), which stimulates the generation of reactive oxygen species in a variety of tissues. Overexpression of renin in Ren2 rats results in hypertension, insulin resistance, and cardiovascular and renal damage. Young (6-7 wk old) insulin-resistant male Ren2 and age-matched insulin sensitive Sprague Dawley rats were treated with the renin inhibitor, aliskiren (50 mg/kg.d by ip injection), or placebo for 21 d. At 21 d, the Ren2 demonstrated insulin resistance with increased islet insulin, Ang II, and reduced total insulin receptor substrate (IRS)-1, IRS-2, and Akt immunostaining. There was increased islet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and subunits (p47(phox) and Rac1) as well as increased nitrotyrosine immunostaining (each P < 0.05). These functional abnormalities were associated with a disordered islet architecture; increased islet-exocrine interface, pericapillary fibrosis, and structurally abnormal mitochondria and content in endocrine and exocrine pancreas. In vivo treatment with aliskiren normalized systemic insulin resistance and islet insulin, Ang II, NADPH oxidase activity/subunits, and nitrotyrosine and improved total IRS-1 and Akt phosphorylation (each P < 0.05) as well as islet/exocrine structural abnormalities. Collectively, these data suggest that pancreatic functional/structural changes are driven, in part, by tissue renin-angiotensin system-mediated increases in NADPH oxidase and reactive oxygen species generation, abnormalities attenuated with direct renin inhibition.
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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.