The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.

Stein, D T; Stevenson, B E; Chester, M W; Basit, M; Daniels, M B; Turley, S D; McGarry, J D

doi:10.1172/jci119546

Cited by 354Pancreatic function and diabetesDiabetes Treatment and ManagementLipid metabolism and biosynthesis

The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.

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Stein, D T, Stevenson, B E, Chester, M W, Basit, M, Daniels, M B, Turley, S D, McGarry, J D·1997·Journal of Clinical Investigation

DOI 10.1172/jci119546PMC PMC508203

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Abstract

Lowering of the elevated plasma FFA concentration in 18- 24-h fasted rats with nicotinic acid (NA) caused complete ablation of subsequent glucose-stimulated insulin secretion (GSIS). Although the effect of NA was reversed when the fasting level of total FFA was maintained by coinfusion of soybean oil or lard oil (plus heparin), the more saturated animal fat proved to be far more potent in enhancing GSIS. We therefore examined the influence of individual fatty acids on insulin secretion in the perfused rat pancreas. When present in the perfusion fluid at 0.5 mM (in the context of 1% albumin), the fold stimulation of insulin release from the fasted pancreas in response to 12.5 mM glucose was as follows: octanoate (C8:0), 3.4; linoleate (C18:2 cis/cis), 5.3; oleate (C18:1 cis), 9.4; palmitate (C16:0), 16. 2; and stearate (C18:0), 21.0. The equivalent value for palmitoleate (C16:1 cis) was 3.1. A cis--> trans switch of the double bond in the C16:1 and C18:1 fatty acids had only a modest, if any, impact on their potency. A similar profile emerged with regard to basal insulin secretion (3 mM glucose). When a subset of these fatty acids was tested in pancreases from fed animals, the same rank order of effectiveness at both basal and stimulatory levels of glucose was seen. The findings reaffirm the essentiality of an elevated plasma FFA concentration for GSIS in the fasted rat. They also show, however, that the insulinotropic effect of individual fatty acids spans a remarkably broad range, increasing and decreasing dramatically with chain length and degree of unsaturation, respectively. Thus, for any given level of glucose, insulin secretion will be influenced greatly not only by the combined concentration of all circulating (unbound) FFA, but also by the makeup of this FFA pool. Both factors will likely be important considerations in understanding the complex interplay between the nature of dietary fat and whole body insulin, glucose, and lipid dynamics.

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Acute exposure to NEFA stimulates insulin secretion in both rodent and human islets, while exposures longer than 24 h are inhibitory.
“Whereas acute exposure to NEFA stimulates insulin secretion in both rodent and human islets (111, 647), exposures for longer than 24h are inhibitory (488).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [647]
The Results (section “In vivo studies”; page not provided) show that fatty acids enhanced glucose-stimulated insulin secretion in perfused rat pancreases. The Discussion says the study examined acute effects in rats; it does not establish the same effect in human islets. The separate citation for exposure longer than 24 hours is not attributed to this paper. (LLM, conf=0.88)
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A fatty acid- dependent step is critically important for both glucose- and non-glucose-stimulated insulin secretion.
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Acute effects of fatty acids on insulin secretion from rat and human islets of Langerhans
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Self-citation

Authors: Stein, D. T., Stevenson, B. E., Chester, M. W., Basit, M., Daniels, M. B., Turley, S. D., & McGarry, J. D.
Affiliations: The University of Texas Southwestern Medical Center (US)
ORCID: McGarry, J D
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1997-07-15
Volume: 100
Issue: 2
Pages: 398-403
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119546
PMC: PMC508203
OpenAlex: W2083278430
Cited by: 352
References: 29
Citations by year: 2026: 1 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 12 · 2018: 9 · 2017: 6 · 2016: 10 · 2015: 12 · 2014: 12 · 2013: 9 · 2012: 12
FWCI: 11.13
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (DK 18573)
Topics: Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords: fatty acids, insulin secretion, glucose-stimulated insulin secretion, fatty acid chain length, degree of unsaturation, nicotinic acid, pancreatic islets, palmitate, oleate, linoleate, octanoate, stearate, palmitoleic acid, cis-trans isomerization, dietary fat, insulin resistance
MeSH terms: Animals, Dietary Fats, Fat Emulsions, Intravenous, Fatty Acids, Fatty Acids, Unsaturated, Glucose, Insulin, Male, Niacin, Pancreas, Perfusion, Soybean Oil, Rats, Sprague-Dawley, Rats

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The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.

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