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AICAR Administration Causes an Apparent Enhancement of Muscle and Liver Insulin Action in Insulin-Resistant High-Fat-Fed Rats
Open accessAbstract
Exercise improves insulin sensitivity. As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) on insulin action in insulin-resistant high-fat-fed (HF) rats. Rats received a subcutaneous injection of 250 mg/kg AICAR (HF-AIC) or saline (HF-Con). The next day, euglycemic-hyperinsulinemic clamp studies were performed. Glucose infusion rate during the clamp was enhanced (50%) in HF-AIC compared with HF-Con rats. Insulin-stimulated glucose uptake was improved in white but not in red quadriceps, whereas glycogen synthesis was improved in both red and white quadriceps of HF-AIC rats. HF-AIC rats also showed increased insulin suppressibility of hepatic glucose output (HGO). AICAR-induced responses in both liver and muscle were accompanied by reduced malonyl-CoA content. Clamp HGO correlated closely with hepatic triglyceride content (r = 0.67, P < 0.01). Thus, a single dose of AICAR leads to an apparent enhancement in whole-body, muscle, and liver insulin action in HF rats that extends beyond the expected time of AMPK activation. Whether altered tissue lipid metabolism mediates AICAR effects on insulin action remains to be determined. Follow-up studies suggest that at least some of the post-AICAR insulin-enhancing effects also occur in normal rats. Independent of this, the results suggest that pharmacological activation of AMPK may have potential in treating insulin-resistant states and type 2 diabetes.
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“indirect SkM CPT1 activation, by the use of AMPK activators ([77](#B77)) or the ACC2 knockout ([1](#B1)), ameliorates insulin-stimulated glucose uptake in rodents.”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [77]
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“The drug 5-aminoimidazole-4-carboxamide (AICA) riboside, which activates AMPK, alleviates metabolic defects of type 2 diabetes and the metabolic syndrome in animal models (15-18).”
From CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations (2004) · cites this paper as [17]
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Metadata
- Authors
- Iglesias, M. A., Ye, J.-M., Frangioudakis, G., Saha, A. K., Tomas, E., Ruderman, N. B., Cooney, G. J., & Kraegen, E. W.
- Affiliations
- Garvan Institute of Medical Research (AU)
- Boston University (US)
- Garvan Institute of Medical Research, Sydney, New South Wales, Australia
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2002-10-01
- Volume
- 51
- Issue
- 10
- Pages
- 2886-2894
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2114339108
- Cited by
- 290
- References
- 50
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 11 · 2017: 9 · 2016: 4 · 2015: 14 · 2014: 21 · 2013: 15 · 2012: 15
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- AICAR, AMPK, insulin resistance, high-fat feeding, insulin sensitivity, skeletal muscle glucose uptake, hepatic glucose production, glycogen synthesis, malonyl-CoA, hepatic triglycerides, type 2 diabetes, physical activity
- MeSH terms
- Aminoimidazole Carboxamide, Animals, Blood Glucose, Body Weight, Dietary Fats, Hypoglycemic Agents, Insulin, Insulin Resistance, Liver, Male, Ribonucleotides, Glucose Clamp Technique, Rats, Wistar, Muscle, Skeletal, Rats
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