ArticleJournal of the American Society of Nephrology : JASN2013
Deletion of the insulin receptor in the proximal tubule promotes hyperglycemia.
Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review.Journal of diabetes research · 2020Pooled it
- Functional Connections Between Insulin and Neurotrophin-3 in Hemodialysis Patients with Type 2 Diabetes.Current issues in molecular biology · 2026Review
- MicroRNA-451 Modulates Autophagy-Related Signaling with Relevance to Renal Fibrosis in an Accelerated Mouse Model of Diabetic Kidney Disease.Current issues in molecular biology · 2026Article
- Coordinated Regulation of Renal Glucose Reabsorption and Gluconeogenesis by mTORC2 and Potassium.Journal of the American Society of Nephrology : JASN · 2025Article
- Association of the Triglyceride-Glucose Index with Body Composition and Laboratory Parameters in Chronic Kidney Disease Stages 3-5.Risk management and healthcare policy · 2025Article
- Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease.Nature communications · 2024Article
- Cocoa and Carob Supplementation, Alone or in Combination with Metformin, Protects against Hepatorenal Injury in Zucker Diabetic Fatty Rats.Nutrients · 2024Article
- Insulin receptor orchestrates kidney antibacterial defenses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Metabolic Fluxes in the Renal Cortex Are Dysregulated In Vivo in Response to High-Fat Diet.Diabetes · 2024Article
- Exploring mechanisms underlying diabetes comorbidities and strategies to prevent vascular complications.Diabetology international · 2024Review
- Triglyceride-glucose index change and chronic kidney disease progression in a Chinese hypertensive population.Frontiers in endocrinology · 2024Article
- Liver or kidney: Who has the oar in the gluconeogenesis boat and when?World journal of diabetes · 2023Review
- Triglyceride-glucose index is associated with the risk of chronic kidney disease progression in type 2 diabetes.Endocrine · 2023Article
- Sex Modulates Response to Renal-Tubule-Targeted Insulin Receptor Deletion in Mice.International journal of molecular sciences · 2023Article
- Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression.Nature communications · 2022Article
- Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver.Nature communications · 2022Article
- Insulin-induced mTOR signaling and gluconeogenesis in renal proximal tubules: A mini-review of current evidence and therapeutic potential.Frontiers in pharmacology · 2022Review
- Novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.Scientific reports · 2021Article
- Renal gluconeogenesis in insulin resistance: A culprit for hyperglycemia in diabetes.World journal of diabetes · 2021Review
- Proximal tubular epithelial insulin receptor mediates high-fat diet-induced kidney injury.JCI insight · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Nearly all renal tubular epithelial cells express insulin receptor. The insulin receptor in the distal tubule appears to modulate BP, but the role of the insulin receptor in the proximal tubule is unknown. Here, we selectively knocked out the insulin receptor from the proximal tubules of mice. Western blotting confirmed a two- to three-fold reduction in renal cortical homogenate insulin receptor-β among knockout mice compared with wild-type littermates. Young knockout mice exhibited a mildly diabetic phenotype, evidenced by higher fasting plasma glucose levels than wild-type mice. Assessments by hyperinsulinemic-euglycemic clamp and a glucose tolerance test revealed no differences in insulin sensitivity or overt pancreatic function, respectively. Renal cortical mRNA expression and enzyme activity of glucose-6-phosphatase, which catalyzes the final step of glucose production, were significantly higher in knockout mice. Taken together, these results support a role for insulin receptor in the proximal tubule in the modulation of systemic glucose levels. Downregulation of the insulin receptor in the proximal tubule, which occurs in insulin-resistant states, may promote hyperglycemia through enhanced gluconeogenesis.
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Registered trials
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