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Cited by 86Pancreatic function and diabetesDiabetes Treatment and ManagementPancreatitis Pathology and Treatment

Fatty acids stimulate insulin secretion from human pancreatic islets at fasting glucose concentrations via mitochondria-dependent and -independent mechanisms

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Cen, Jing, Sargsyan, Ernest, Bergsten, Peter·2016·Nutrition & Metabolism
DOI 10.1186/s12986-016-0119-5PMC PMC5006523
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Abstract

BACKGROUND: Free fatty acids (FFAs) acutely stimulate insulin secretion from pancreatic islets. Conflicting results have been presented regarding this effect at non-stimulatory glucose concentration, however. The aim of our study was to investigate how long-chain FFAs affect insulin secretion from isolated human pancreatic islets in the presence of physiologically fasting glucose concentrations and to explore the contribution of mitochondria to the effects on secretion. METHODS: Insulin secretion from human pancreatic islets was measured from short-term static incubation or perfusion system at fasting glucose concentration (5.5 mM) with or without 4 different FFAs (palmitate, palmitoleate, stearate, and oleate). The contribution of mitochondrial metabolism to the effects of fatty acid-stimulated insulin secretion was explored. RESULTS: The average increase in insulin secretion, measured from statically incubated and dynamically perifused human islets, was about 2-fold for saturated free fatty acids (SFAs) (palmitate and stearate) and 3-fold for mono-unsaturated free fatty acids (MUFAs) (palmitoleate and oleate) compared with 5.5 mmol/l glucose alone. Accordingly, MUFAs induced 50 % and SFAs 20 % higher levels of oxygen consumption compared with islets exposed to 5.5 mmol/l glucose alone. The effect was due to increased glycolysis. When glucose was omitted from the medium, addition of the FFAs did not affect oxygen consumption. However, the FFAs still stimulated insulin secretion from the islets although secretion was more than halved. The mitochondria-independent action was via fatty acid metabolism and FFAR1/GPR40 signaling. CONCLUSIONS: The findings suggest that long-chain FFAs acutely induce insulin secretion from human islets at physiologically fasting glucose concentrations, with MUFAs being more potent than SFAs, and that this effect is associated with increased glycolytic flux and mitochondrial respiration.

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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 [111]

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Authors
Cen, J., Sargsyan, E., & Bergsten, P.
Affiliations
Uppsala University (SE)
Corresponding author
Sargsyan, Ernest
ORCID
Venue
Nutrition & Metabolism
Publisher
Springer Science and Business Media LLC
Published
2016-08-30
Volume
13
Issue
1
Pages
59-59
ISSN
1743-7075 (ISSN-L)
DOI
10.1186/s12986-016-0119-5
PMC
PMC5006523
OpenAlex
W2509671353
Cited by
86
References
1
Citations by year
2026: 2 · 2025: 10 · 2024: 10 · 2023: 14 · 2022: 13 · 2021: 11 · 2020: 5 · 2019: 10 · 2018: 8 · 2017: 3
FWCI
7.75
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nutrition & Metabolism (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
Funders
  • European Commission (BE) (279 153)
  • Swedish Diabetes Association (DIA 2013043)
  • Stiftelsen Familjen Ernfors Fond (150 430)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Keywords
free fatty acids, insulin secretion, pancreatic islets, fasting blood glucose, long-chain fatty acids, palmitate, palmitoleic acid, stearate, oleate, monounsaturated fatty acids, saturated fatty acids, mitochondrial respiration, glycolysis, oxygen consumption, GPR40, free fatty acid receptor 1, fatty acid metabolism

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