ArticleJournal of translational medicine2016
The GLP-1 receptor agonists exenatide and liraglutide activate Glucose transport by an AMPK-dependent mechanism.
Article in Journal of translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 100 citations in OpenAlex.
- Lixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance.The Journal of clinical endocrinology and metabolism · 2019Trial
- Blood-Brain Glucose Transfer in Alzheimer's disease: Effect of GLP-1 Analog Treatment.Scientific reports · 2017Trial
- Integrating bile acid metabolism into precision nutrition strategies for improved swine performance.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF.International journal of molecular sciences · 2026Review
- The Role of TXNIP in Skeletal Muscle Physiology and Related Diseases: Current Perspectives.Journal of inflammation research · 2026Review
- The expanding role of semaglutide: beyond glycemic control.Journal of diabetes and metabolic disorders · 2025Review
- Engineered GLP-1R-targeting nanoplatforms: multimodal therapeutics in human diseases.Journal of nanobiotechnology · 2025Review
- Approaching therapy of Alzheimer's disease via the antidiabetic drug liraglutide-a study with streptozotocin intracerebroventricularly treated Wistar rats.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Impact of Incretin-Based Therapy on Skeletal Muscle Health.Medicina (Kaunas, Lithuania) · 2025Review
- Localized Semaglutide Injection for Hyperinsulinemia-Induced Lymphatic Dysfunction: A Narrative Review Proposing a Promising Metabolic Perspective for Lymphedema Therapy.Advanced pharmaceutical bulletin · 2025Review
- Targeting Sarcopenia in CKD: The Emerging Role of GLP-1 Receptor Agonists.International journal of molecular sciences · 2025Review
- Gastrointestinal Motility Effects of GLP-1 Receptor Agonists.Current gastroenterology reports · 2025Review
- Unlocking the multifaceted roles of GLP-1: Physiological functions and therapeutic potential.Toxicology reports · 2025Review
- Role of GLP‑1 receptor agonists in sepsis and their therapeutic potential in sepsis‑induced muscle atrophy (Review).International journal of molecular medicine · 2025Review
- Liraglutide Attenuates FFA-Induced Retinal Pigment Epithelium Dysfunction via AMPK Activation and Lipid Homeostasis Regulation in ARPE-19 Cells.International journal of molecular sciences · 2025Article
- Dual and Triple Gut Peptide Agonists on the Horizon for the Treatment of Type 2 Diabetes and Obesity. An Overview of Preclinical and Clinical Data.Current obesity reports · 2025Review
- Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis.International journal of molecular sciences · 2025Review
- Liraglutide and denatonium benzoate attenuate T2DM-induced metabolic, neurological, and testicular changes in rats: Targeting oxidative stress, inflammation, and BCRP transporter.Journal of molecular histology · 2025Article
- Effects of Hypoglycemic Agents on The Musculoskeletal System: A Comprehensive Review.Drug design, development and therapy · 2025Review
- Incretin-Based Therapies: A Promising Approach for Modulating Oxidative Stress and Insulin Resistance in Sarcopenia.Journal of bone metabolism · 2024Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisPotentiation of glucose-induced insulin secretion is the main mechanism of exenatide (EXE) antidiabetic action, however, increased glucose utilization by peripheral tissues has been also reported. We here studied the effect of EXE on glucose uptake by skeletal muscle cells.
methods2-deoxy-glucose (2DG) uptake and intracellular signal pathways were measured in rat L6 skeletal muscle myotubes exposed to 100 nmol/l EXE for up to 48 h. Mechanisms of EXE action were explored by inhibiting AMPK activity with compound C (CC, 40 μmol/l) or siRNAs (2 μmol/l).
resultsTime course experiments show that EXE increases glucose uptake up to 48 h achieving its maximal effect, similar to that induced by insulin, after 20 min (2- vs 2.5-fold-increase, respectively). Differently from insulin, EXE does not stimulate: (i) IR β-subunit- and IRS1 tyrosine phosphorylation and binding to p85 regulatory subunit of PI-3kinase; (ii) AKT activation; and (iii) ERK1/2 and JNK1/2 phosphorylation. Conversely, EXE increases phosphorylation of α-subunit of AMPK at Thr172 by 2.5-fold (p < 0.01). Co-incubation of EXE and insulin does not induce additive effects on 2DG-uptake. Inhibition of AMPK with CC, and reduction of AMPK protein expression by siRNA, completely abolish EXE-induced 2DG-uptake. Liraglutide, another GLP-1 receptor agonist, also stimulates AMPK phosphorylation and 2DG-uptake. Moreover, EXE stimulates 2DG-uptake also by L6 myotubes rendered insulin-resistant with methylglyoxal. Finally, EXE also induces glucose transporter Glut-4 translocation to the plasma membrane. CONCLUSIONS/
interpretationIn L6 myotubes, EXE and liraglutide increase glucose uptake in an insulin-independent manner by activating AMPK.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.