ArticleJCI insight2018
PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.
- Pooled it
- Unveiling the Mechanism of Protective Effects of Tanshinone as a New Fighter Against Cardiovascular Diseases: A Systematic Review.Cardiovascular toxicology · 2024Pooled it
- Pharmacodynamic effects of direct AMP kinase activation in humans with insulin resistance and non-alcoholic fatty liver disease: A phase 1b study.Cell reports. Medicine · 2021Trial
- AMPK-Directed Therapeutics for MASLD: Mechanistic Rationale, Activator Classes, and Clinical Translation.International journal of molecular sciences · 2026Review
- AMPK Therapy-A Little Goes A Long Way.Cells · 2026Review
- Metformin Redirects Autophagy from Bulk Turnover to Mitochondrial Clearance.bioRxiv : the preprint server for biology · 2026Article
- CD8Science China. Life sciences · 2026Review
- Association of glucose metabolism with advanced cardiovascular-kidney-metabolic syndrome and prediction model development in type 2 diabetes mellitus.BMC endocrine disorders · 2026Article
- Aerobic glycolysis drives differentiation of unilocular adipocytes.Journal of lipid research · 2026Article
- AMPK: an enzyme that may be effective in cancer and metabolic diseases.Discover oncology · 2025Review
- PRKAA2 mediates the pathogenesis of metabolic dysfunction-associated steatotic liver disease via PI3K/AKT signaling pathway.Human genomics · 2025Article
- Nanoparticle delivery of AMPK activator 991 prevents its toxicity and improves muscle homeostasis in Duchenne muscular dystrophy.Molecular therapy. Methods & clinical development · 2025Article
- AMPK activator ATX-304 reduces oxidative stress and improves MASLD via metabolic switching.JCI insight · 2025Article
- Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy.Journal of medicinal chemistry · 2025Review
- Ebastine-mediated destabilization of E3 ligase MKRN1 protects against metabolic dysfunction-associated steatohepatitis.Cellular and molecular life sciences : CMLS · 2025Article
- Research progress on the role of FGF21 in insulin resistance.Frontiers in endocrinology · 2025Review
- AMPK signaling in osteoarthritis: from mechanisms to targeted therapeutics.Frontiers in pharmacology · 2025Review
- AMPK as a mediator of tissue preservation: time for a shift in dogma?Nature reviews. Endocrinology · 2024Review
- AMPK pathway: an emerging target to control diabetes mellitus and its related complications.Journal of diabetes and metabolic disorders · 2024Review
- Myeloid AMPK signaling restricts fibrosis but is not required for metformin improvements during CDAHFD-induced NASH in mice.Journal of lipid research · 2024Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced β cell stress, and promoted β cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro- and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.
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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.