Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models
Abstract
AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To understand better the physiological role of the catalytic AMPK subunit isoforms, we generated two knockout mouse models with the α1 (AMPKα1−/−) and α2 (AMPKα2−/−) catalytic subunit genes deleted. No defect in glucose homoeostasis was observed in AMPKα1−/− mice. On the other hand, AMPKα2−/− mice presented high plasma glucose levels and low plasma insulin concentrations in the fed period and during the glucose tolerance test. Nevertheless, in isolated AMPKα2−/− pancreatic islets, glucose-stimulated insulin secretion was not affected. Surprisingly, AMPKα2−/− mice were insulin-resistant and had reduced muscle glycogen synthesis as assessed in vivo by the hyperinsulinaemic euglycaemic clamp procedure. Reduction of insulin sensitivity and glycogen synthesis were not dependent on the lack of AMPK in skeletal muscle, since mice expressing a dominant inhibitory mutant of AMPK in skeletal muscle were not affected and since insulin-stimulated glucose transport in incubated muscles in vitro was normal in AMPKα2−/− muscles. Furthermore, AMPKα2−/− mice have a higher sympathetic tone, as shown by increased catecholamine urinary excretion. Increased adrenergic tone could explain both decreased insulin secretion and insulin resistance observed in vivo in AMPKα2−/− mice. We suggest that the α2 catalytic subunit of AMPK plays a major role as a fuel sensor by modulating the activity of the autonomous nervous system in vivo.
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AMPK α1 KO mice have normal AMPK T172 phosphorylation in skeletal muscle despite reduced α1 activity.
“In contrast, AMPK α1 KO mice have normal AMPK T172 phosphorylation in skeletal muscle despite reduced α1 activity, showing that α2 AMPK is the predominant isoform contributing to AMPK activity in skeletal muscle [35].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [35]
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“No evidence indicates inflammation in AMPKa2 mice, either [43].”
BackgroundSelf-citationAMP-activated kinase is a regulator of fibroblast growth factor 23 production
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“AMP-activated protein kinase (AMPK) is a master metabolic regulator and an important target for drug development against diabetes, obesity, and other diseases [1–5].”
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“The involvement of AMPK in diabetes mellitus is demonstrated by insulin resistance, with associated high levels of plasma glucose and low levels of insulin in mice with ablated AMPK (Viollet et al., 2003).”
Background
- Authors
- Viollet, B., Andreelli, F., Jørgensen, S. B., Perrin, C., Flamez, D., Mu, J., Wojtaszewski, J. F. P., Schuit, F. C., Birnbaum, M., Richter, E., Burcelin, R., & Vaulont, S.
- Affiliations
- Institut Cochin (FR)
- Institut Cochin, Dpt GDPM, 24 rue du faubourg Saint-Jacques 75014 Paris, France
- University of Copenhagen (DK)
- Centre National de la Recherche Scientifique (FR)
- Diabetes Research Center, Brussels, Belgium
- Howard Hughes Medical Institute (US)
- Corresponding author
- Viollet, B.
- Vaulont, S.
- ORCID
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2003-02-01
- Volume
- 31
- Issue
- 1
- Pages
- 216-219
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- OpenAlex
- W2060836453
- Cited by
- 241
- References
- 0
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 2 · 2022: 8 · 2021: 13 · 2020: 8 · 2019: 8 · 2018: 11 · 2017: 10 · 2016: 12 · 2015: 8 · 2014: 19 · 2013: 19 · 2012: 21
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- AMPK, glucose homeostasis, insulin resistance, glucose-stimulated insulin secretion, pancreatic islets, muscle glycogen synthesis, insulin sensitivity, sympathetic nervous system, catecholamine excretion, knockout mice
- MeSH terms
- Animals, Glucose Tolerance Test, Glycogen, Mice, Transgenic, Models, Biological, Multienzyme Complexes, Mutation, Protein Serine-Threonine Kinases, Mice, Knockout, Muscle, Skeletal, Catalytic Domain, Mice, AMP-Activated Protein Kinases
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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