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Diabetes 53:S166-S171, 2004
© 2004 by the American Diabetes Association, Inc.

Section IV: Lipid Modulators of Islet Function

Acute {omega}-3 Fatty Acid Enrichment Selectively Reverses High-Saturated Fat Feeding-Induced Insulin Hypersecretion But Does Not Improve Peripheral Insulin Resistance

Mark J. Holness, Nicholas D. Smith, Gemma K. Greenwood, and Mary C. Sugden

From the Centre for Diabetes and Metabolic Medicine, Bart’s and the London, Queen Mary’s School of Medicine and Dentistry, University of London, London, U.K

In rats fed a high-saturated fat diet, replacement of a small percentage of total fatty acids with long-chain {omega}-3 fatty acids from fish oil for the duration of high-fat feeding prevents the development of insulin resistance. We investigated the effect of acute (24-h) modulation of dietary fat composition on glucose-stimulated insulin secretion (GSIS) in rats made insulin resistant by high-saturated fat feeding for 4 weeks. Insulin secretion after an intravenous glucose challenge was greatly increased by high-saturated fat feeding. Glucose tolerance was minimally perturbed, demonstrating insulin hypersecretion compensated for insulin resistance. The effect of high-saturated fat feeding to enhance GSIS was retained in perifused islets, such that glucose stimulus-secretion coupling was potentiated. Acute replacement of 7% of dietary fatty acids with long-chain {omega}-3 fatty acids reversed insulin hypersecretion in vivo, and the effect of long-term high-saturated fat feeding to enhance insulin secretion by perifused islets was also completely reversed. Although a hyperbolic relationship existed between insulin secretion and action in the high-saturated fat and control groups, lowered insulin secretion in the acute fish oil-supplemented group was not accompanied by improved insulin action, and glucose tolerance was adversely affected. Our studies are important because they demonstrate that hyperinsulinemia can be rapidly reversed via the dietary provision of small amounts of long-chain {omega}-3 fatty acids. However, this "insulin sparing" action of acute dietary long-chain {omega}-3 fatty acids occurs in the absence of an acute improvement in insulin sensitivity and therefore at the expense of maintenance of glucose tolerance.

Address correspondence and reprint requests to Dr. M.J. Holness, Centre for Diabetes and Metabolic Medicine, Medical Sciences Bldg., Queen Mary, University of London, Mile End Rd., London E1 4NS, U.K. E-mail: m.j.holness{at}qmul.ac.uk


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Copyright © 2004 by the American Diabetes Association.