Holness Mark J, Greenwood Gemma K, Smith Nicholas D, Sugden Mary C
Department of Diabetes and Metabolic Medicine, Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London, London E1 4NS, United Kingdom.
Endocrinology. 2003 Sep;144(9):3958-68. doi: 10.1210/en.2003-0479.
In healthy individuals, peripheral insulin resistance evoked by dietary saturated lipid can be accompanied by increased insulin secretion such that glucose tolerance is maintained. Substitution of long-chain omega-3 fatty acids for a small percentage of dietary saturated fat prevents insulin resistance in response to high-saturated fat feeding. We substituted a small amount (7%) of dietary lipid with long-chain omega-3 fatty acids during 4 wk of high-saturated fat feeding to investigate the relationship between amelioration of insulin resistance and glucose-stimulated insulin secretion (GSIS). We demonstrate that, despite dietary delivery of saturated fat throughout, this manipulation prevents high-saturated fat feeding-induced insulin resistance with respect to peripheral glucose disposal and reverses insulin hypersecretion in response to glucose in vivo. Effects of long-chain omega-3 fatty acid enrichment to lower GSIS were also observed in perifused islets suggesting a direct effect on islet function. However, long-chain omega-3 fatty acid enrichment led to hepatic insulin resistance with respect to suppression of glucose output and impaired glucose tolerance in vivo. Our data demonstrate that the insulin response to glucose is suppressed to a greater extent than whole-body insulin sensitivity is enhanced by enrichment of a high-saturated fat diet with long-chain omega-3 fatty acids. Additionally, reduced GSIS despite glucose intolerance suggests that either long-chain omega-3 fatty acids directly impair the beta-cell response to saturated fat such that insulin secretion cannot be augmented to normalize glucose tolerance or beta-cell compensatory hypersecretion represents a response to insulin resistance at the level of peripheral glucose disposal but not endogenous glucose production.
在健康个体中，饮食中饱和脂质引起的外周胰岛素抵抗可伴有胰岛素分泌增加，从而维持葡萄糖耐量。用一小部分长链ω-3脂肪酸替代饮食中的饱和脂肪可预防因高饱和脂肪饮食引起的胰岛素抵抗。我们在4周的高饱和脂肪饮食期间，用长链ω-3脂肪酸替代了少量（7%）的饮食脂质，以研究胰岛素抵抗改善与葡萄糖刺激的胰岛素分泌（GSIS）之间的关系。我们证明，尽管整个饮食过程中都摄入了饱和脂肪，但这种操作可预防高饱和脂肪饮食诱导的外周葡萄糖处置方面的胰岛素抵抗，并逆转体内对葡萄糖的胰岛素分泌过多。在灌注胰岛中也观察到长链ω-3脂肪酸富集降低GSIS的作用，提示对胰岛功能有直接影响。然而，长链ω-3脂肪酸富集导致肝脏在抑制葡萄糖输出方面出现胰岛素抵抗，并损害体内葡萄糖耐量。我们的数据表明，高饱和脂肪饮食中添加长链ω-3脂肪酸后，对葡萄糖的胰岛素反应受到的抑制程度大于全身胰岛素敏感性的增强程度。此外，尽管存在葡萄糖不耐受但GSIS降低，这表明要么长链ω-3脂肪酸直接损害β细胞对饱和脂肪的反应，使得胰岛素分泌无法增加以恢复葡萄糖耐量正常化，要么β细胞代偿性分泌过多代表了对外周葡萄糖处置水平而非内源性葡萄糖产生水平的胰岛素抵抗的一种反应。
