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

The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.

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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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
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
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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