ArticleJournal of the American Society of Nephrology : JASN2012
Hyperglycemia and renin-dependent hypertension synergize to model diabetic nephropathy.
Article in Journal of the American Society of Nephrology : JASN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- The predictive potential of surrogate indicators of insulin resistance for type 2 diabetic kidney disease.Frontiers in endocrinology · 2026Article
- Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review.Plants (Basel, Switzerland) · 2025Review
- Immune inflammation and metabolic interactions in the pathogenesis of diabetic nephropathy.Frontiers in endocrinology · 2025Review
- Rodent models to study type 1 and type 2 diabetes induced human diabetic nephropathy.Molecular biology reports · 2023Review
- Sodium-glucose cotransporter 2 inhibition does not improve the acute pressure natriuresis response in rats with type 1 diabetes.Experimental physiology · 2023Article
- Blood pressure-independent renoprotective effects of small interference RNA targeting liver angiotensinogen in experimental diabetes.British journal of pharmacology · 2023Article
- Plasminogen Deficiency and Amiloride Mitigate Angiotensin II-Induced Hypertension in Type 1 Diabetic Mice Suggesting Effects Through the Epithelial Sodium Channel.Journal of the American Heart Association · 2020Article
- NOX4-dependent regulation of ENaC in hypertension and diabetic kidney disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Revisiting Experimental Models of Diabetic Nephropathy.International journal of molecular sciences · 2020Review
- Article
- Impact of sex on diabetic nephropathy and the renal transcriptome in UNx db/db C57BLKS mice.Physiological reports · 2019Article
- Renal lesions in leptin receptor-deficient medaka (Journal of toxicologic pathology · 2019Article
- A new, easily generated mouse model of diabetic kidney fibrosis.Scientific reports · 2019Article
- Animal Models of Hypertension: A Scientific Statement From the American Heart Association.Hypertension (Dallas, Tex. : 1979) · 2019Review
- Impaired pressure natriuresis and non-dipping blood pressure in rats with early type 1 diabetes mellitus.The Journal of physiology · 2019Article
- Inflammation and Immunity Pathways Regulate Genetic Susceptibility to Diabetic Nephropathy.Diabetes · 2018Article
- An integrative systems biology approach for precision medicine in diabetic kidney disease.Diabetes, obesity & metabolism · 2018Review
- Progressive Renal Disease Established by Renin-Coding Adeno-Associated Virus-Driven Hypertension in Diverse Diabetic Models.Journal of the American Society of Nephrology : JASN · 2018Article
- Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications.Scientific reports · 2018Article
- Modelling diabetic nephropathy in mice.Nature reviews. Nephrology · 2018Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Rodent models exhibit only the earliest features of human diabetic nephropathy, which limits our ability to investigate new therapies. Hypertension is a prerequisite for advanced diabetic nephropathy in humans, so its rarity in typical rodent models may partly explain their resistance to nephropathy. Here, we used the Cyp1a1mRen2 rat, in which the murine renin-2 gene is incorporated under the Cytochrome P4501a1 promoter. In this transgenic strain, administration of low-dose dietary indole-3-carbinol induces moderate hypertension. In the absence of hypertension, streptozotocin-induced diabetes resulted in a 14-fold increase in albuminuria but only mild changes in histology and gene expression despite 28 weeks of marked hyperglycemia. In the presence of induced hypertension, hyperglycemia resulted in a 500-fold increase in albuminuria, marked glomerulosclerosis and tubulointerstitial fibrosis, and induction of many of the same pathways that are upregulated in the tubulointerstitium in human diabetic nephropathy. In conclusion, although induction of diabetes alone in rodents has limited utility to model human diabetic nephropathy, renin-dependent hypertension and hyperglycemia synergize to recapitulate many of the clinical, histological, and gene expression changes observed in humans.
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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 Socratic graph.