ArticleThe Journal of biological chemistry2021
Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus.
Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- Metabolic-inflammatory memory: the common pathological basis and therapeutic targets of metabolic syndrome.Reviews in endocrine & metabolic disorders · 2026Review
- Metformin in Diabetes and Beyond: Therapeutic Mechanisms, Lactic Acidosis, Organ-Specific Effects, and Nanotechnology-Based Delivery Strategies.Current medical science · 2026Review
- High palmitate induces ferroptosis in RIN-m5f cells via miR-3584-5p-mediated suppression of AQP7.Scientific reports · 2026Article
- A convective transport-enhanced multi-organoid device for therapeutic modeling of the liver-pancreas axis in obesity.Theranostics · 2026Article
- AQP7 deficiency drives adipose tissue remodeling and disrupts homeostasis.npj metabolic health and disease · 2025Article
- Aquaporins in lipid metabolism: functions and regulation in health and disease.Lipids in health and disease · 2025Review
- Potential of Pandan Root and Teak Leaf Extracts in Managing Maternal Hyperglycemia During Pregnancy: Comparative Efficacy and Mechanistic Insights.International journal of molecular sciences · 2025Article
- Positive feedback loop between MAPK and aquaporin 7 regulates autophagy and apoptosis induced by palmitate in RIN-m5f cells.FEBS open bio · 2025Article
- ERK1/2 gene expression and hypomethylation of Alu and LINE1 elements in patients with type 2 diabetes with and without cataract: Impact of hyperglycemia-induced oxidative stress.Journal of diabetes investigation · 2025Article
- Article
- Cardioprotective Effects of Phlorizin on Hyperlipidemia-induced Myocardial Injury: Involvement of Suppression in Pyroptosis via Regulating HK1/NLRP3/Caspase-1 Signaling Pathway.Applied biochemistry and biotechnology · 2025Article
- Network pharmacology-based study on the mechanism of Tangfukang formula against type 2 diabetes mellitus.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Single and Combined Impact of Semaglutide, Tirzepatide, and Metformin on β-Cell Maintenance and Function Under High-Glucose-High-Lipid Conditions: A Comparative Study.International journal of molecular sciences · 2025Article
- Exploration of Pharmacological Mechanisms of Dapagliflozin against Type 2 Diabetes Mellitus through PI3K-Akt Signaling Pathway based on Network Pharmacology Analysis and Deep Learning Technology.Current computer-aided drug design · 2025Article
- Impact of high-fructose diet and metformin on histomorphological and molecular parameters of reproductive organs and vaginal microbiota of female rat.Scientific reports · 2024Article
- The Important Role of Aquaglyceroporin 7 in Health and Disease.Biomolecules · 2024Review
- Antidiabetic and Anti-Inflammatory Effect ofPharmaceuticals (Basel, Switzerland) · 2024Article
- RedRibbon: A new rank-rank hypergeometric overlap for gene and transcript expression signatures.Life science alliance · 2024Article
- Advances in polysaccharides of natural source of anti-diabetes effect and mechanism.Molecular biology reports · 2024Review
- Inhibition of Sat1 alleviates myocardial ischemia-reperfusion injury through regulation of ferroptosis via MAPK/ERK pathway.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. Although accumulated evidence has shed light on the consequences of metformin action, the precise mechanisms of its action, especially in the pancreas, are not fully understood. Aquaporin 7 (AQP7) acts as a critical regulator of intraislet glycerol content, which is necessary for insulin production and secretion. The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets. We used an in vivo model of high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic β-cells (INS-1 cells) damaged by hyperglycemia and hyperlipidemia. Our data showed that AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in vivo and in vitro in response to hyperglycemia and hyperlipidemia. T2DM rats treated with metformin demonstrated a reduction in blood glucose levels and increased regeneration of pancreatic β-cells. In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro. Overexpression of AQP7 increased glycerol influx into INS-1 cells, whereas inhibition of AQP7 reduced glycerol influx, thereby decreasing subsequent insulin secretion. Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression and promoting glycerol influx into pancreatic β-cells and subsequent insulin secretion in T2DM.
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