Cited by 348Pancreatic function and diabetesDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

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Effects of Free Fatty Acids (FFA) on Glucose Metabolism: Significance for Insulin Resistance and Type 2 Diabetes

Boden, G.·2003·Experimental and Clinical Endocrinology & Diabetes

DOI 10.1055/s-2003-39781

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Abstract

Most obese individuals have elevated plasma levels of free fatty acids (FFA) which are known to cause peripheral (muscle) insulin resistance. They do this by inhibiting insulin-stimulated glucose uptake and glycogen synthesis. The mechanism involves intramyocellular accumulation of diacylglycerol and activation of protein kinase C. FFAs also cause hepatic insulin resistance. They do this by inhibiting insulin-mediated suppression of glycogenolysis. On the other hand, FFAs support between 30 and 50 % of basal insulin secretion and potentiate glucose-stimulated insulin secretion. The insulin stimulatory action of FFAs is responsible for the fact that the vast majority ( approximately 80 %) of obese insulin resistant people do not develop type 2 diabetes. They are able to compensate for their FFA mediated insulin resistance with increased FFA mediated insulin secretion. Individuals who are unable to do this (probably for genetic reasons) eventually develop type 2 diabetes. FFAs have recently been shown to activate the IkappaB/NFkappaB pathway which is involved in many inflammatory processes. Thus, elevated plasma levels of FFAs are not only a major cause of insulin resistance in skeletal muscle and liver but may, in addition, play a role in the pathogenesis of coronary artery disease.

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ResultInfluential
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RETRACTED ARTICLE: GLP-1 receptor agonist lixisenatide protects against high free fatty acids-induced oxidative stress and inflammatory response
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Retracted
Hyperglycemia after protein ingestion concurrent with injection of a GLP-1 receptor agonist in rats: a possible role for dietary peptides
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Background

Authors: Boden, G.
Affiliations: Temple University (US)
Corresponding author: Boden, G.
Venue: Experimental and Clinical Endocrinology & Diabetes
Publisher: Georg Thieme Verlag KG
Published: 2003-06-04
Volume: 111
Issue: 03
Pages: 121-124
ISSN: 0947-7349 (ISSN-L)
1439-3646
DOI: 10.1055/s-2003-39781
OpenAlex: W121967333
Cited by: 348
References: 0
Citations by year: 2026: 6 · 2025: 9 · 2024: 20 · 2023: 17 · 2022: 26 · 2021: 30 · 2020: 17 · 2019: 17 · 2018: 15 · 2017: 16 · 2016: 9 · 2015: 12 · 2014: 14 · 2013: 13 · 2012: 18
FWCI: 14.70
Type: journal article
Language: en
Open access: closed
Locations: Experimental and Clinical Endocrinology & Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ag007988-10, 5r01ag015363-05)
National Institute on Aging (AG15363, R01-AG07988)
National Center for Research Resources (2 M01-RR-349)
NIH Clinical Center
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: free fatty acids, insulin resistance, type 2 diabetes, glucose metabolism, skeletal muscle insulin signaling, hepatic insulin resistance, insulin secretion, diacylglycerol, protein kinase C, glycogen synthesis, glycogenolysis, obesity, NF-κB signaling, inflammation, coronary artery disease
MeSH terms: Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Glucose, Humans, Insulin Resistance, Liver, Obesity

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Effects of Free Fatty Acids (FFA) on Glucose Metabolism: Significance for Insulin Resistance and Type 2 Diabetes

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