ArticleAmerican journal of physiology. Renal physiology2016
Metformin, an AMPK activator, stimulates the phosphorylation of aquaporin 2 and urea transporter A1 in inner medullary collecting ducts.
Article in American journal of physiology. Renal physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 55 citations in OpenAlex.
- Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial.Clinical journal of the American Society of Nephrology : CJASN · 2022Trial
- Effects of sildenafil, metformin, and simvastatin on ADH-independent urine concentration in healthy volunteers.Physiological reports · 2018Trial
- GLUT9b- and ABCG2-mediated collecting duct urate transport uncovers a vasopressin-independent mechanism of renal water reabsorption.The Journal of clinical investigation · 2026Article
- Urea Transporters in Cancer: Emerging Roles and Their Clinical Implications.Biomedicines · 2025Review
- Ribosomal s6 kinase is a mediator of aquaporin-2 S256 phosphorylation and membrane accumulation after EGFR inhibition with erlotinib.American journal of physiology. Renal physiology · 2025Article
- Tissue Distribution, Expression and Regulation of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Disruption of mitochondrial electron transport impairs urinary concentration via AMPK-dependent suppression of aquaporin 2.JCI insight · 2024Article
- Central and nephrogenic diabetes insipidus: updates on diagnosis and management.Frontiers in endocrinology · 2024Review
- Real-life use of tolvaptan in ADPKD: a retrospective analysis of a large Canadian cohort.Scientific reports · 2023Article
- Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2.Kidney diseases (Basel, Switzerland) · 2023Article
- Metformin Inhibits NaFrontiers in physiology · 2022Article
- Aquaporin 2 regulation: implications for water balance and polycystic kidney diseases.Nature reviews. Nephrology · 2021Review
- An AMPK activator as a therapeutic option for congenital nephrogenic diabetes insipidus.JCI insight · 2021Article
- The Role of Vasopressin V2 Receptor in Drug-Induced Hyponatremia.Frontiers in physiology · 2021Review
- Metformin and Inhibition of Transforming Growth Factor-Beta StimulateTissue engineering. Part A · 2020Article
- PKA-independent vasopressin signaling in renal collecting duct.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Targeting the Trafficking of Kidney Water Channels for Therapeutic Benefit.Annual review of pharmacology and toxicology · 2020Review
- Predictors of Mortality in Patients with Chronic Heart Failure: Is Hyponatremia a Useful Clinical Biomarker?International journal of general medicine · 2020Article
- Role of PKC and AMPK in hypertonicity-stimulated water reabsorption in rat inner medullary collecting ducts.American journal of physiology. Renal physiology · 2019Article
- Vasopressin-aquaporin-2 pathway: recent advances in understanding water balance disorders.F1000Research · 2019Review
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7 authors at 1 institution in 1 country.
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Abstract
Nephrogenic diabetes insipidus (NDI) is characterized by production of very large quantities of dilute urine due to an inability of the kidney to respond to vasopressin. Congenital NDI results from mutations in the type 2 vasopressin receptor (V2R) in ∼90% of families. These patients do not have mutations in aquaporin-2 (AQP2) or urea transporter UT-A1 (UT-A1). We tested adenosine monophosphate kinase (AMPK) since it is known to phosphorylate another vasopressin-sensitive transporter, NKCC2 (Na-K-2Cl cotransporter). We found AMPK expressed in rat inner medulla (IM). AMPK directly phosphorylated AQP2 and UT-A1 in vitro. Metformin, an AMPK activator, increased phosphorylation of both AQP2 and UT-A1 in rat inner medullary collecting ducts (IMCDs). Metformin increased the apical plasma membrane accumulation of AQP2, but not UT-A1, in rat IM. Metformin increased both osmotic water permeability and urea permeability in perfused rat terminal IMCDs. These findings suggest that metformin increases osmotic water permeability by increasing AQP2 accumulation in the apical plasma membrane but increases urea permeability by activating UT-A1 already present in the membrane. Lastly, metformin increased urine osmolality in mice lacking a V2R, a mouse model of congenital NDI. We conclude that AMPK activation by metformin mimics many of the mechanisms by which vasopressin increases urine-concentrating ability. These findings suggest that metformin may be a novel therapeutic option for congenital NDI due to V2R mutations.
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