The DOI matches its Crossref record; 28 of the 29 references it cites were found in a registry or an index.
The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.
Open accessAbstract
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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“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]
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Citations
Cites
Dietary influences on serum lipids and lipoproteins.
Grundy, S. M., & Denke, M. (1990) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42625-2 · Cited by 1,044
Lee, Y., Hirose, H., Ohneda, M., Johnson, J. H., McGarry, J., & Unger, R. H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10878 · Cited by 832
Self-citationPrentki, M., Vischer, S., Glennon, M. C., Regazzi, R., Deeney, J. T., & Corkey, B. E. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42624-5 · Cited by 442
Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat.
Stein, D. T., Esser, V., Stevenson, B. E., Lane, K. E., Whiteside, J. H., Daniels, M. B., Chen, S., & McGarry, J. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118727 · Cited by 371
Self-citationUnbound free fatty acid levels in human serum.
Richieri, G. V., & Kleinfeld, A. M. (1995) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39899-0 · Cited by 320
Effects of a 48-h Fat Infusion on Insulin Secretion and Glucose Utilization
Boden, G., Chen, X., Rosner, J., & Barton, M. (1995) · Diabetes · doi:10.2337/diab.44.10.1239 · Cited by 271
Zhou, Y. P. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.80.5.1584 · Cited by 243
Paolisso, G., Gambardella, A., Amato, L., Tortoriello, R., D'Amore, A., Varricchio, M., & D'Onofrio, F. (1995) · Diabetologia · doi:10.1007/bf00401761 · Cited by 217
Parker, D., Weiss, S. T., Troisi, R. J., Cassano, P. A., Vokonas, P., & Landsberg, L. (1993) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/58.2.129 · Cited by 212
Hamilton, J. G. C., & Comai, K. (1988) · Lipids · doi:10.1007/bf02535281 · Cited by 208
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McGarry, J. D. (2002) · Diabetes · doi:10.2337/diabetes.51.1.7 · Cited by 1,435
Self-citationLewis, G. F., Carpentier, A. C., Adeli, K., & Giacca, A. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.2.0461 · Cited by 1,370
Boden, G., & Shulman, G. I. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.32.s3.3.x · Cited by 1,300
Holland, W. L., Brozinick, J. T., Wang, L.-P., Hawkins, E. D., Sargent, K. M., Liu, Y., Narra, K., Hoehn, K. L., Knotts, T. A., Siesky, A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.01.002 · Cited by 1,232
Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism
Cao, H., Gerhold, K. A., Mayers, J. R., Wiest, M. M., Watkins, S. M., & Hotamışlıgil, G. S. (2008) · Cell · doi:10.1016/j.cell.2008.07.048 · Cited by 1,174
Metadata
- 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
- Published
- 1997-07-15
- Volume
- 100
- Issue
- 2
- Pages
- 398-403
- ISSN
- 0021-9738 (ISSN-L)
- 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 › Endocrinology, Diabetes and Metabolism › 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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