The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation
The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation
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DOI：
10.1172/jci119546
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发表时间：
1997-07-15
影响因子：
15.9
通讯作者：
McGarry, JD
中科院分区：
文献类型：
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作者：
Stein, DT;Stevenson, BE;McGarry, JD
用烟酸 (NA) 降低 18-24 小时禁食大鼠中升高的血浆 FFA 浓度，导致随后的葡萄糖刺激的胰岛素分泌 (GSIS) 完全消除。尽管当通过混用大豆油或猪油（加肝素）维持总 FFA 的空腹水平时，NA 的影响被逆转，但事实证明，更饱和的动物脂肪在增强 GSIS 方面更为有效，因此我们研究了单个脂肪酸对灌注大鼠胰腺中胰岛素分泌的影响，当灌注液中存在 0.5 mM（在 1% 白蛋白的情况下）时，对禁食胰腺中胰岛素释放的刺激倍数增加对 12.5 mM 葡萄糖的响应如下：辛酸 (C-8:0)，3.4；亚油酸酯（C-18:2 顺式/顺式），5.3；油酸酯（C-18:1 顺式），9,4；棕榈酸酯（C-16:0），16.2；和硬脂酸酯 (C-18:0)，21.0，棕榈油酸酯（C-16:1 顺式）的当量值为 3.1，C-16:1 和 C-18:1 脂肪酸中双键的顺式→反式转换对其效力仅产生适度（如果有的话）影响，在基础胰岛素分泌（3 mM 葡萄糖）方面出现类似的情况，当这些脂肪酸的子集在研究结果再次证实了禁食大鼠血浆 FFA 浓度升高对于 GSIS 的重要性。然而，它们还表明，单个脂肪酸的促胰岛素作用跨越了一个非常广泛的范围，分别随着链长和不饱和度的增加和减少而显着增加和减少。因此，对于任何给定的葡萄糖水平，胰岛素分泌不仅受到脂肪酸组合浓度的影响，而且会受到很大的影响。所有循环（未结合）FFA，以及该 FFA 池的构成，这两个因素可能是理解膳食脂肪性质与全身胰岛素、葡萄糖和脂质动态之间复杂相互作用的重要考虑因素。
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 (C-8:0), 3.4; linoleate (C-18:2 cis/cis), 5.3; oleate (C-18:1 cis), 9,4; palmitate (C-16:0), 16.2; and stearate (C-18:0), 21.0, The equivalent value for palmitoleate (C-16:1 cis) was 3.1, A cis-->trans switch of the double bond in the C-16:1 and C-18:1 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.