AN AMINO-ACID SUBSTITUTION IN THE HUMAN INTESTINAL FATTY-ACID-BINDING PROTEIN IS ASSOCIATED WITH INCREASED FATTY-ACID-BINDING, INCREASED FAT OXIDATION, AND INSULIN-RESISTANCE
AN AMINO-ACID SUBSTITUTION IN THE HUMAN INTESTINAL FATTY-ACID-BINDING PROTEIN IS ASSOCIATED WITH INCREASED FATTY-ACID-BINDING, INCREASED FAT OXIDATION, AND INSULIN-RESISTANCE
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DOI：
10.1172/jci117778
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发表时间：
1995-03-01
影响因子：
15.9
通讯作者：
PROCHAZKA, M
中科院分区：
文献类型：
--
作者：
BAIER, LJ;SACCHETTINI, JC;PROCHAZKA, M
肠道脂肪酸结合蛋白基因座（FABP 2）进行了研究，作为一个可能的遗传因素，在确定胰岛素的作用，在皮马印度人口。FABP 2第54位密码子的多态性导致一个编码丙氨酸的等位基因（频率0.71）和一个编码苏氨酸的等位基因（频率0.29）。与丙氨酸编码等位基因纯合子的Pimas相比，苏氨酸编码等位基因纯合子或杂合子的Pimas具有较高的平均空腹血浆胰岛素浓度，较低的平均胰岛素刺激葡萄糖摄取率，较高的平均胰岛素对口服葡萄糖和混合餐的反应，以及较高的平均脂肪氧化率。由于FABP 2苏氨酸编码等位基因被发现与体内胰岛素抵抗和脂肪氧化增加有关，我们进一步分析了FABP 2基因产物的潜在功能差异。用纯化的重组蛋白进行的微量滴定热研究表明，含苏氨酸的蛋白质对长链脂肪酸的亲和力比含丙氨酸的蛋白质大两倍。我们的结论是，含苏氨酸的蛋白质可能会增加肠道对膳食脂肪酸的吸收和/或加工，从而增加脂肪氧化，这已被证明会降低胰岛素的作用。
The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimulated glucose uptake rate, a higher mean insulin response to oral glucose and a mixed meal, and a higher mean fat oxidation rate compared with Pimas who were homozygous for the alanine-encoding allele. Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences. Titration microcalorimetry studies with purified recombinant protein showed that the threonine-containing protein had a twofold greater affinity for long-chain fatty acids than the alanine-containing protein. We conclude that the threonine-containing protein may increase absorption and/or processing of dietary fatty acids by the intestine and thereby increase fat oxidation, which has been shown to reduce insulin action.