ArticleAmerican journal of physiology. Renal physiology2011
Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 95 citations in OpenAlex.
- Effect of Metformin on Renal Function After Primary Percutaneous Coronary Intervention in Patients Without Diabetes Presenting with ST-elevation Myocardial Infarction: Data from the GIPS-III Trial.Cardiovascular drugs and therapy · 2015 · on this mapTrial
- The Effect of Renal Ischemia/Reperfusion on the Renal Expression of Epithelial Sodium Channels in Rat: Possible Role of Neural Precursor Cell-Expressed Developmentally Down-Regulated Protein (Nedd4-2).Kidney & blood pressure research · 2026Article
- Kidney cell response to acute cardiorenal and isolated kidney ischemia-reperfusion injury.Physiological genomics · 2025Article
- Individuals Diagnosed With Type 2 Diabetes Mellitus and the Status of Vitamin B12 Deficiency: A Review.Cureus · 2024Review
- Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes.World journal of diabetes · 2023Review
- Ketogenic Diet and Ketone Bodies against Ischemic Injury: Targets, Mechanisms, and Therapeutic Potential.International journal of molecular sciences · 2023Review
- A bioinspired carbon monoxide delivery system prevents acute kidney injury and the progression to chronic kidney disease.Redox biology · 2022Article
- Effects of metformin, rapamycin, and resveratrol on cellular metabolism of canine primary fibroblast cells isolated from large and small breeds as they age.GeroScience · 2021Article
- Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells.Scientific reports · 2021Article
- Metformin ameliorates the severity of experimental Alport syndrome.Scientific reports · 2021Article
- The role of AMPK in regulation of NaJournal of muscle research and cell motility · 2021Review
- Metformin Preconditioning and Postconditioning to Reduce Ischemia Reperfusion Injury in an Isolated Ex Vivo Rat and Porcine Kidney Normothermic Machine Perfusion Model.Clinical and translational science · 2021Article
- Critical Role for AMPK in Metabolic Disease-Induced Chronic Kidney Disease.International journal of molecular sciences · 2020Review
- Activation of AMPK under Hypoxia: Many Roads Leading to Rome.International journal of molecular sciences · 2020Review
- Mechanisms involved in AMPK-mediated deposition of tight junction components to the plasma membrane.American journal of physiology. Cell physiology · 2020Article
- Roles of AMP-Activated Protein Kinase (AMPK) in Mammalian Reproduction.Frontiers in cell and developmental biology · 2020Review
- Irisin Pretreatment Protects Kidneys against Acute Kidney Injury Induced by Ischemia/Reperfusion via Upregulating the Expression of Uncoupling Protein 2.BioMed research international · 2020Article
- Metabolic Flexibility and Innate Immunity in Renal Ischemia Reperfusion Injury: The Fine Balance Between Adaptive Repair and Tissue Degeneration.Frontiers in immunology · 2020Review
- Reciprocal Association between the Apical Junctional Complex and AMPK: A Promising Therapeutic Target for Epithelial/Endothelial Barrier Function?International journal of molecular sciences · 2019Review
- Metformin modulates immune cell infiltration into the kidney during unilateral ureteral obstruction in mice.Physiological reports · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
Alterations in epithelial cell polarity and in the subcellular distributions of epithelial ion transport proteins are key molecular consequences of acute kidney injury and intracellular energy depletion. AMP-activated protein kinase (AMPK), a cellular energy sensor, is rapidly activated in response to renal ischemia, and we demonstrate that its activity is upregulated by energy depletion in Madin-Darby canine kidney (MDCK) cells. We hypothesized that AMPK activity may influence the maintenance or recovery of epithelial cell organization in mammalian renal epithelial cells subjected to energy depletion. MDCK cells were ATP depleted through a 1-h incubation with antimycin A and 2-deoxyglucose. Immunofluoresence localization demonstrated that this regimen induces mislocalization of the Na-K-ATPase from its normal residence at the basolateral plasma membrane to intracellular vesicular compartments. When cells were pretreated with the AMPK activator metformin before energy depletion, basolateral localization of Na-K-ATPase was preserved. In MDCK cells in which AMPK expression was stably knocked down with short hairpin RNA, preactivation of AMPK with metformin did not prevent Na-K-ATPase redistribution in response to energy depletion. In vivo studies demonstrate that metformin activated renal AMPK and that treatment with metformin before renal ischemia preserved cellular integrity, preserved Na-K-ATPase localization, and led to reduced levels of neutrophil gelatinase-associated lipocalin, a biomarker of tubular injury. Thus AMPK may play a role in preserving the functional integrity of epithelial plasma membrane domains in the face of energy depletion. Furthermore, pretreatment with an AMPK activator before ischemia may attenuate the severity of renal tubular injury in the context of acute kidney injury.
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