ArticleNature communications2016
AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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Who cites it
69 citing papers in PubMed, 147 citations in OpenAlex.
- Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy.FEBS open bio · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Posttranslational modifications of phosphodiesterase type 4 enzymes represent novel points for therapeutic targeting.The FEBS journal · 2025Review
- Beyond diabetes: harnessing the power of metformin in burn care.Critical care (London, England) · 2025Review
- Autosomal Dominant Polycystic Kidney Disease: From Pathogenesis to Organoid Disease Models.Biomedicines · 2025Review
- Targeting Ferroptosis in Parkinson's: Repurposing Diabetes Drugs as a Promising Treatment.International journal of molecular sciences · 2025Review
- Review
- PDE4B Missense Variant Increases Susceptibility to Post-traumatic Stress Disorder-Relevant Phenotypes in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Imeglimin enhances glucagon secretion through an indirect mechanism and improves fatty liver in high-fat, high-sucrose diet-fed mice.Journal of diabetes investigation · 2024Article
- Contrasting views on the role of AMPK in autophagy.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- The impact of glucagon to support postabsorptive glucose flux and glycemia in healthy rats and its attenuation in male Zucker diabetic fatty rats.American journal of physiology. Endocrinology and metabolism · 2024Article
- TGF-β1 Signaling Impairs Metformin Action on Glycemic Control.International journal of molecular sciences · 2024Article
- Examining the clinical relevance of metformin as an antioxidant intervention.Frontiers in pharmacology · 2024Article
- Catalpol attenuates hepatic glucose metabolism disorder and oxidative stress in triptolide-induced liver injury by regulating the SIRT1/HIF-1α pathway.International journal of biological sciences · 2024Article
- Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives.Molecular medicine (Cambridge, Mass.) · 2023Review
- Hepatic p38α MAPK controls gluconeogenesis via FOXO1 phosphorylation at S273 during glucagon signalling in mice.Diabetologia · 2023Article
- Review
- Modulation of cardiac cAMP signaling by AMPK and its adjustments in pressure overload-induced myocardial dysfunction in rat and mouse.PloS one · 2023Article
- Article
- Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model.International journal of molecular sciences · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated protein kinase (AMPK) via direct inhibition of adenylate cyclase by AMP. Here we show that incubation of hepatocytes with the small-molecule AMPK activator 991 decreases glucagon-stimulated cAMP accumulation, cAMP-dependent protein kinase (PKA) activity and downstream PKA target phosphorylation. Moreover, incubation of hepatocytes with 991 increases the Vmax of cyclic nucleotide phosphodiesterase 4B (PDE4B) without affecting intracellular adenine nucleotide concentrations. The effects of 991 to decrease glucagon-stimulated cAMP concentrations and activate PDE4B are lost in hepatocytes deleted for both catalytic subunits of AMPK. PDE4B is phosphorylated by AMPK at three sites, and by site-directed mutagenesis, Ser304 phosphorylation is important for activation. In conclusion, we provide a new mechanism by which AMPK antagonizes hepatic glucagon signalling via phosphorylation-induced PDE4B activation.
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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.