Grill V, Qvigstad E
Department of Internal Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Br J Nutr. 2000 Mar;83 Suppl 1:S79-84. doi: 10.1017/s0007114500000994.
It has long been recognized that acute elevation of non-esterified fatty acids (NEFA) stimulates insulin secretion to a moderate extent both in vitro and in vivo. The effects of longer-term exposure to elevated fatty acids have, however, been investigated only recently. Our own studies in the rat have documented the time dependence of NEFA effects, with inhibition of glucose-induced insulin secretion being apparent after 6-24 h in vivo exposure to Intralipid or in vitro exposure to palmitate, oleate and octanoate. Evidence indicates that the inhibitory effects are coupled to fatty acid oxidation in B-cells, with ensuing reduction in glucose oxidation, in parallel with diminished activity of the pyruvate dehydrogenase enzyme. These findings were essentially confirmed in human pancreatic islets. In the db/db mouse, a model of type 2 diabetes with obesity, evidence was obtained for elevated NEFA playing a significant role in decreased glucose-induced insulin secretion. Evidence also indicates that elevated NEFA inhibit insulin biosynthesis and increase the proinsulin:insulin ratio of secretion. Results on experimentally induced elevations of NEFA in non-diabetic and diabetic humans are thus far inconclusive. Further studies are needed to ascertain the impact of elevated NEFA on insulin secretion in clinical settings.
长期以来，人们已经认识到非酯化脂肪酸（NEFA）的急性升高在体外和体内均能在一定程度上刺激胰岛素分泌。然而，长期暴露于升高的脂肪酸的影响直到最近才得到研究。我们在大鼠身上进行的研究记录了NEFA作用的时间依赖性，在体内暴露于英脱利匹特或体外暴露于棕榈酸、油酸和辛酸6 - 24小时后，葡萄糖诱导的胰岛素分泌受到抑制。有证据表明，抑制作用与β细胞中的脂肪酸氧化相关，随之葡萄糖氧化减少，同时丙酮酸脱氢酶的活性降低。这些发现基本上在人胰岛中得到了证实。在db/db小鼠（一种伴有肥胖的2型糖尿病模型）中，有证据表明升高的NEFA在葡萄糖诱导的胰岛素分泌减少中起重要作用。也有证据表明升高的NEFA抑制胰岛素生物合成并增加胰岛素原与胰岛素的分泌比例。到目前为止，关于在非糖尿病和糖尿病患者中实验性诱导NEFA升高的结果尚无定论。需要进一步研究以确定在临床环境中升高的NEFA对胰岛素分泌的影响。
