Cited by 292Metabolism, Diabetes, and CancerAdipose Tissue and MetabolismNatural Antidiabetic Agents Studies

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AICAR Administration Causes an Apparent Enhancement of Muscle and Liver Insulin Action in Insulin-Resistant High-Fat-Fed Rats

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Iglesias, Miguel A., Ye, Ji-Ming, Frangioudakis, Georgia, Saha, Asish K., Tomas, Eva, Ruderman, Neil B., Cooney, Gregory J., Kraegen, Edward W.·2002·Diabetes

DOI 10.2337/diabetes.51.10.2886

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Abstract

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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Modulation nutritionnelle du métabolisme lipidique et de la mitochondrie (structure et fonction) : effet des lipides et des polyphénols
Aoun, M. (2011) · theses.fr (ABES) · doi:10.70675/ecc42ac5z114bz4ef6z9a62z03e344922f78
The AMPK signaling pathway in cell metabolism and human diseases
Zhang, Z., Gu, Y., He, H., Qiao, S., Shao, Y., 龙先铭, Huang, J., Zhang, L., & Zhou, F. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02790-6
BindingDB Entry 50025542: Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase.
BindingDB (2010) · UC San Diego · doi:10.7270/q2bc3zbq
BindingDB Entry 50000315: Hit-to-Lead Optimization and Discovery of 5-((5-([1,1'-Biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of Benzimidazole-Based Activators of AMP-Activated Protein Kinase.
BindingDB (2019) · UC San Diego · doi:10.7270/q2v69n0q
Obesity and Adipokines
Rogers, N. H., Obin, M. S., & Greenherg, A. S. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-400-1_4
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Fazakerley, D. J. (2010) · The University of Bath Online Publications Store (The University of Bath)
Stoffwechsel des Herzens bei Diabetes
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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: Iglesias, Miguel A.
Ye, Ji-Ming
Frangioudakis, Georgia
Saha, Asish K.
Ruderman, Neil B.
Cooney, Gregory J.
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2002-10-01
Volume: 51
Issue: 10
Pages: 2886-2894
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.51.10.2886
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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AICAR Administration Causes an Apparent Enhancement of Muscle and Liver Insulin Action in Insulin-Resistant High-Fat-Fed Rats

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