• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Jul 15, 1997; 100(2): 398–403.
PMCID: PMC508203

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


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.

Full Text

The Full Text of this article is available as a PDF (184K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Greenough WB, 3rd, Crespin SR, Steinberg D. Hypoglycaemia and hyperinsulinaemia in response to raised free-fatty-acid levels. Lancet. 1967 Dec 23;2(7530):1334–1336. [PubMed]
  • Seyffert WA, Jr, Madison LL. Physiologic effects of metabolic fuels on carbohydrate metabolism. I. Acute effect of elevation of plasma free fatty acids on hepatic glucose output, peripheral glucose utilization, serum insulin, and plasma glucagon levels. Diabetes. 1967 Nov;16(11):765–776. [PubMed]
  • Crespin SR, Greenough WB, 3rd, Steinberg D. Stimulation of insulin secretion by long-chain free fatty acids. A direct pancreatic effect. J Clin Invest. 1973 Aug;52(8):1979–1984. [PMC free article] [PubMed]
  • Balasse EO, Ooms HA. Role of plasma free fatty acids in the control of insulin secretion in man. Diabetologia. 1973 Apr;9(2):145–151. [PubMed]
  • Tamarit-Rodríguez J, Vara E, Tamarit J. Starvation-induced changes of palmitate metabolism and insulin secretion in isolated rat islets stimulated by glucose. Biochem J. 1984 Jul 15;221(2):317–324. [PMC free article] [PubMed]
  • Boden G, Chen X, Rosner J, Barton M. Effects of a 48-h fat infusion on insulin secretion and glucose utilization. Diabetes. 1995 Oct;44(10):1239–1242. [PubMed]
  • Stein DT, Esser V, Stevenson BE, Lane KE, Whiteside JH, Daniels MB, Chen S, McGarry JD. Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat. J Clin Invest. 1996 Jun 15;97(12):2728–2735. [PMC free article] [PubMed]
  • Chen S, Ogawa A, Ohneda M, Unger RH, Foster DW, McGarry JD. More direct evidence for a malonyl-CoA-carnitine palmitoyltransferase I interaction as a key event in pancreatic beta-cell signaling. Diabetes. 1994 Jul;43(7):878–883. [PubMed]
  • Hamilton JG, Comai K. Rapid separation of neutral lipids, free fatty acids and polar lipids using prepacked silica Sep-Pak columns. Lipids. 1988 Dec;23(12):1146–1149. [PubMed]
  • Malaisse WJ, Malaisse-Lagae F, Wright PH. Effect of fasting upon insulin secretion in the rat. Am J Physiol. 1967 Oct;213(4):843–848. [PubMed]
  • Grey NJ, Goldring S, Kipnis DM. The effect of fasting, diet, and actinomycin D on insulin secretion in the rat. J Clin Invest. 1970 May;49(5):881–889. [PMC free article] [PubMed]
  • Burch PT, Trus MD, Berner DK, Leontire A, Zawalich KC, Matschinsky FM. Adaptation of glycolytic enzymes: glucose use and insulin release in rat pancreatic islets during fasting and refeeding. Diabetes. 1981 Nov;30(11):923–928. [PubMed]
  • Richieri GV, Kleinfeld AM. Unbound free fatty acid levels in human serum. J Lipid Res. 1995 Feb;36(2):229–240. [PubMed]
  • Opara EC, Garfinkel M, Hubbard VS, Burch WM, Akwari OE. Effect of fatty acids on insulin release: role of chain length and degree of unsaturation. Am J Physiol. 1994 Apr;266(4 Pt 1):E635–E639. [PubMed]
  • Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney JT, Corkey BE. Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion. J Biol Chem. 1992 Mar 25;267(9):5802–5810. [PubMed]
  • Berne C. The metabolism of lipids in mouse pancreatic islets. The oxidation of fatty acids and ketone bodies. Biochem J. 1975 Dec;152(3):661–666. [PMC free article] [PubMed]
  • Warnotte C, Gilon P, Nenquin M, Henquin JC. Mechanisms of the stimulation of insulin release by saturated fatty acids. A study of palmitate effects in mouse beta-cells. Diabetes. 1994 May;43(5):703–711. [PubMed]
  • Grundy SM, Denke MA. Dietary influences on serum lipids and lipoproteins. J Lipid Res. 1990 Jul;31(7):1149–1172. [PubMed]
  • Maron DJ, Fair JM, Haskell WL. Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and Staff. Circulation. 1991 Nov;84(5):2020–2027. [PubMed]
  • Mayer EJ, Newman B, Quesenberry CP, Jr, Selby JV. Usual dietary fat intake and insulin concentrations in healthy women twins. Diabetes Care. 1993 Nov;16(11):1459–1469. [PubMed]
  • Parker DR, Weiss ST, Troisi R, Cassano PA, Vokonas PS, Landsberg L. Relationship of dietary saturated fatty acids and body habitus to serum insulin concentrations: the Normative Aging Study. Am J Clin Nutr. 1993 Aug;58(2):129–136. [PubMed]
  • Hannah JS, Howard BV. Dietary fats, insulin resistance, and diabetes. J Cardiovasc Risk. 1994 Jun;1(1):31–37. [PubMed]
  • McGarry JD. Disordered metabolism in diabetes: have we underemphasized the fat component? J Cell Biochem. 1994;55 (Suppl):29–38. [PubMed]
  • Rasmussen O, Lauszus FF, Christiansen C, Thomsen C, Hermansen K. Differential effects of saturated and monounsaturated fat on blood glucose and insulin responses in subjects with non-insulin-dependent diabetes mellitus. Am J Clin Nutr. 1996 Feb;63(2):249–253. [PubMed]
  • Lee Y, Hirose H, Ohneda M, Johnson JH, McGarry JD, Unger RH. Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10878–10882. [PMC free article] [PubMed]
  • Zhou YP, Grill V. Long term exposure to fatty acids and ketones inhibits B-cell functions in human pancreatic islets of Langerhans. J Clin Endocrinol Metab. 1995 May;80(5):1584–1590. [PubMed]
  • Paolisso G, Gambardella A, Amato L, Tortoriello R, D'Amore A, Varricchio M, D'Onofrio F. Opposite effects of short- and long-term fatty acid infusion on insulin secretion in healthy subjects. Diabetologia. 1995 Nov;38(11):1295–1299. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...