ArticleScientific reports2024
Dapagliflozin improves skeletal muscle insulin sensitivity through SIRT1 activation induced by nutrient deprivation state.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of SGLT2 inhibitors on body composition and potential sarcopenia-related outcomes in type 2 diabetes mellitus: a network meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Bridging Glycemic and Lipid Control: Effects of Dapagliflozin in Co-Morbid Diabetes and Heart Failure – A Randomized Controlled TrialEndocrine, metabolic & immune disorders drug targets · 2026Trial
- Identification of novel small molecules as potential SGLT2 inhibitors through combined virtual screening and experimental validation.Molecular diversity · 2026Article
- Dapagliflozin Protects Cardiomyocytes against Doxorubicin-Induced Toxicity by Modulating Sirtuin 1/Sirtuin 3 and Ferroptosis Pathway.ACS pharmacology & translational science · 2026Article
- Dapagliflozin-intermittent fasting combination maximizes weight and metabolic regulation through AMPK/sirtuins/clock genes and gut microbiota signaling in high-fat diet-induced obesity: a novel anti-obesity approach.Cell & bioscience · 2026Article
- The SGLT2 inhibitor empagliflozin promotes increased fatty acid oxidation in skeletal muscle cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Alcohol-Mediated Skeletal Muscle Adaptations and Their Impact on Comorbidities.The American journal of pathology · 2026Review
- Exploring Dapagliflozin's Influence on Autophagic Flux in Mania-like Behaviour: Insights from the LKB1/AMPK/LC3 Pathway in a Mouse Model.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
Lipid peroxidation and mitochondrial damage impair insulin sensitivity in skeletal muscle. Sirtuin-1 (SIRT1) protects mitochondria and activates under energy restriction. Dapagliflozin (Dapa) is an antihyperglycaemic agent that belongs to the sodium-glucose cotransporter-2 (SGLT2) inhibitors. Evidence shows that Dapa can induce nutrient deprivation effects, providing additional metabolic benefits. This study investigates whether Dapa can trigger nutrient deprivation to activate SIRT1 and enhance insulin sensitivity in skeletal muscle. We treated diet-induced obese (DIO) mice with Dapa and measured metabolic parameters, lipid accumulation, oxidative stress, mitochondrial function, and glucose utilization in skeletal muscle. β-hydroxybutyric acid (β-HB) was intervened in C2C12 myotubes. The role of SIRT1 was verified by RNA interference. We found that Dapa treatment induced nutrient deprivation state and reduced lipid deposition and oxidative stress, improved mitochondrial function and glucose tolerance in skeletal muscle. The same positive effects were observed after β-HB intervening for C2C12 myotubes, and the promoting effects on glucose utilization were diminished by SIRT1 RNA interference. Thus, Dapa promotes a nutrient deprivation state and enhances skeletal muscle insulin sensitivity via SIRT1 activation. In this study, we identified a novel hypoglycemic mechanism of Dapa and the potential mechanistic targets.
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