Effects of free fatty acids (FFA) on glucose metabolism: Significance for insulin resistance and type 2 diabetes
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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Obesity-related type 2 diabetes patients often have elevated plasma FFAs, because of either increased amounts of FFAs released from large amounts of adipose tissue or impaired FFA clearance.
“Obesity-related type 2 diabetes patients often have elevated plasma FFAs, because of either increased amounts of FFAs released from large amounts of adipose tissue or impaired FFA clearance [258].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [258]
Changes in NEFA levels are central to the development of insulin resistance and metabolic disease.
“Alterations in non-esterified (i.e. free) fatty acid (NEFA) levels play a central role in the pathogenesis of insulin resistance and the development of metabolic diseases [8, 9].”
From Sleep restriction increases free fatty acids in healthy men (2015) · cites this paper as [9]
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- 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
- 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 › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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