Cited by 601Diet, Metabolism, and DiseaseDiabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and Cancer

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Development of Muscle Insulin Resistance After Liver Insulin Resistance in High-Fat–Fed Rats

Kraegen, Edward W, Clark, Peter W, Jenkins, Arthur B, Daley, Eugene A, Chisholm, Donald J, Storlien, Leonard H·1991·Diabetes

DOI 10.2337/diab.40.11.1397

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Abstract

Muscle and hepatic insulin resistance are two major defects of non-insulin-dependent diabetes mellitus. Dietary factors may be important in the etiology of insulin resistance. We studied progressive changes in the development of high-fat–diet–induced insulin resistance in tissues of the adult male Wistar rat. In vivo insulin action was compared 3 days and 3 wk after isocaloric synthetic high-fat or high-starch feeding (59 and 10% cal as fat, respectively). Basal and insulin-stimulated glucose metabolism were assessed in the conscious 5- to 7-h fasted state with the euglycemic clamp (600 pM insulin) with a [3-3H]-glucose infusion. Fat feeding significantly reduced suppressibility of hepatic glucose output by insulin after both 3 days and 3 wk of diet (P < 0.01). However, a significant impairment of insulin-mediated peripheral glucose disposal was only present after 3 wk of diet. Further in vivo [3H]-2-deoxyglucose uptake studies supported this finding and demonstrated adipose but not muscle insulin resistance after 3 days of high-fat feeding. Muscle triglyceride accumulation due to fat feeding was not significant at 3 days but had doubled by 3 wk in red muscle (P < 0.001) compared with starch-fed controls. By 3 wk, high-fat—fed animals had developed significant glucose intolerance. We concludethat fat feeding induces insulin resistance in liver and adipose tissue before skeletal muscle with early metabolic changes favoring an oversupply of energy substrate to skeletal muscle relative to metabolic needs. This may generate later muscle insulin resistance.

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Authors: Kraegen, E. W., Clark, P. W., Jenkins, A. B., Daley, E. A., Chisholm, D. J., & Storlien, L. H.
Affiliations: Garvan Institute of Medical Research (AU)
ORCID: Clark, Peter W
Jenkins, Arthur B
Chisholm, Donald J
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1991-11-01
Volume: 40
Issue: 11
Pages: 1397-1403
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diab.40.11.1397
OpenAlex: W2049881486
Cited by: 601
References: 0
Citations by year: 2026: 1 · 2025: 3 · 2024: 10 · 2023: 11 · 2022: 14 · 2021: 7 · 2020: 13 · 2019: 22 · 2018: 18 · 2017: 17 · 2016: 37 · 2015: 22 · 2014: 37 · 2013: 31 · 2012: 27
FWCI: 2.59
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: National Health and Medical Research Council
National Medical Research Council
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: insulin resistance, high-fat diet, hepatic insulin resistance, skeletal muscle insulin resistance, adipose tissue insulin resistance, hepatic glucose production, impaired glucose tolerance, type 2 diabetes, dietary fat
MeSH terms: Animals, Dietary Fats, Glucose, Insulin, Insulin Resistance, Liver, Male, Muscles, Rats, Inbred Strains, Starch, Triglycerides, Rats

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Development of Muscle Insulin Resistance After Liver Insulin Resistance in High-Fat–Fed Rats

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