ArticleBritish journal of pharmacology2017
Activation of AMP-activated protein kinase by metformin ablates angiotensin II-induced endoplasmic reticulum stress and hypertension in mice in vivo.
Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Metabolic and Anti-Inflammatory Effects of Berberine-Rationale for Its Therapeutic Potential in Polycystic Ovary Syndrome.International journal of molecular sciences · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Exploring the Effects of Metformin on the Body via the Urine Proteome.Biomolecules · 2025Article
- Could the Propionic Acid Treatment in Combination with Metformin be Safe for the Small Intestine of Diabetic Rats?Endocrine, metabolic & immune disorders drug targets · 2024Article
- Metformin Impedes Oxidation of LDL In Vitro.Pharmaceutics · 2023Article
- Molecular Mechanism Underlying Role of the XBP1s in Cardiovascular Diseases.Journal of cardiovascular development and disease · 2022Review
- Down-regulation of AMPK/PPARδ signalling promotes endoplasmic reticulum stress-induced endothelial dysfunction in adult rat offspring exposed to maternal diabetes.Cardiovascular research · 2022Article
- Protection by metformin against severe Covid-19: An in-depth mechanistic analysis.Diabetes & metabolism · 2022Review
- Roles of ATP and SERCA in the Regulation of Calcium Turnover in Unloaded Skeletal Muscles: Current View and Future Directions.International journal of molecular sciences · 2022Review
- Functional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19.Reviews in endocrine & metabolic disorders · 2022Review
- Effect of Propionic Acid on Diabetes-Induced Impairment of Unfolded Protein Response Signaling and Astrocyte/Microglia Crosstalk in Rat Ventromedial Nucleus of the Hypothalamus.Neural plasticity · 2022Article
- Endoplasmic reticulum as a target in cardiovascular diseases: Is there a role for flavonoids?Frontiers in pharmacology · 2022Review
- Uncovering antiobesity-related hypertension targets and mechanisms of metformin, an antidiabetic medication.Bioengineered · 2021Article
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- Curcumin attenuates angiotensin II-induced podocyte injury and apoptosis by inhibiting endoplasmic reticulum stress.FEBS open bio · 2020Article
- Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib.International journal of molecular sciences · 2020Article
- Amelioration of metabolic syndrome by metformin associates with reduced indices of low-grade inflammation independently of the gut microbiota.American journal of physiology. Endocrinology and metabolism · 2019Article
- AMPK: a balancer of the renin-angiotensin system.Bioscience reports · 2019Review
- Sulfenamide and Sulfonamide Derivatives of Metformin - A New Option to Improve Endothelial Function and Plasma Haemostasis.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
background and purposeMetformin, one of the most frequently prescribed medications for type 2 diabetes, reportedly exerts BP-lowering effects in patients with diabetes. However, the effects and underlying mechanisms of metformin on BP in non-diabetic conditions remain to be determined. The aim of the present study was to determine the effects of metformin on angiotensin II (Ang II) infusion-induced hypertension in vivo. EXPERIMENTAL APPROACH: The effects of metformin on BP were investigated in wild-type (WT) C57BL/6J mice and in mice lacking AMP-activated protein kinase α2 (AMPKα2) mice with or without Ang II infusion. Also, the effect of metformin on Ang II-induced endoplasmic reticulum (ER) stress was explored in cultured human vascular smooth muscle cells (hVSMCs). KEY
resultsMetformin markedly reduced BP in Ang II-infused WT mice but not in AMPKα2-deficient mice. In cultured hVSMCs, Ang II treatment resulted in inactivation of AMPK, as well as the subsequent induction of spliced X-box binding protein-1, phosphorylation of eukaryotic translation initiation factor 2α and expression of glucose-regulated protein 78 kDa, representing three well-characterized ER stress biomarkers. Moreover, AMPK activation by metformin ablated Ang II-induced ER stress in hVSMCs. Mechanistically, metformin-activated AMPKα2 suppressed ER stress by increasing phospholamban phosphorylation. CONCLUSION AND IMPLICATIONS: Metformin alleviates Ang II-triggered hypertension in mice by activating AMPKα2, which mediates phospholamban phosphorylation and inhibits Ang II-induced ER stress in vascular smooth muscle cells.
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