High fat diet induced insulin resistance and glucose intolerance are gender-specific in IGF-1R heterozygous mice.
High fat diet induced insulin resistance and glucose intolerance are gender-specific in IGF-1R heterozygous mice.
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DOI：
10.1016/j.bbrc.2011.08.123
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发表时间：
2011-09-30
影响因子：
3.1
通讯作者：
Adamo, Martin L.
中科院分区：
文献类型：
--
作者：
Garg, Neha;Thakur, Sachin;McMahan, C. Alex;Adamo, Martin L.
基因与环境的相互作用在2型糖尿病的发病机制中起关键作用。由于影响胎儿生长的遗传和环境变量，低出生体重与成年后患2型糖尿病和代谢紊乱的易感性增加有关。临床研究表明，胰岛素样生长因子1 （IGF-1）基因的多态性或IGF-1和IGF-1受体（IGF-1R）基因的杂合突变导致IGF-1作用降低，与低出生体重和出生后生长有关。缺乏IGF-1R等位基因之一（Igf1r+/−）的小鼠在出生后生长减少10%，并随着年龄的增长出现葡萄糖耐受不良和胰岛素抵抗。为了研究不良环境因素是否会加速代谢综合征的发生，我们对雄性和雌性Igf1r+/−和野生型（WT）对照小鼠进行了短时间的高脂肪饮食（HFD）喂养干预。在两种基因型的男性中，HFD导致胰岛素抵抗、高血糖和糖耐量受损，而在女性中，仅在Igf1r+/−基因型中观察到糖尿病加重，因此表明肥胖对由IGF-1作用降低引起的糖尿病遗传易感性的影响存在性别二态性。
Interactions between genes and environment play a critical role in the pathogenesis of Type 2 diabetes. Low birth weight, due to genetic and environmental variables affecting fetal growth, is associated with increased susceptibility to the development of type 2 diabetes and metabolic disorders in adulthood. Clinical studies have shown that polymorphisms in the Insulin-like growth factor 1 (IGF-1) gene or heterozygous mutations in IGF-1 and IGF-1 receptor (IGF-1R) genes, resulting in reduced IGF-1 action, are associated with low birth weight and post-natal growth. Mice lacking one of the IGF-1R alleles (Igf1r+/−) exhibit a 10% reduction in post-natal growth, and develop glucose intolerance and insulin resistance as they age. To investigate whether adverse environmental factors could accelerate the onset of the metabolic syndrome, we conducted a short duration intervention of high fat diet (HFD) feeding in male and female Igf1r+/− and wild-type (WT) control mice. The HFD resulted in insulin resistance, hyperglycemia, and impaired glucose tolerance in males of both genotypes whereas in females exacerbated diabetes was observed only in the Igf1r+/− genotype, thus suggesting a sexual dimorphism in the influence of obesity on the genetic predisposition to diabetes caused by reduced IGF-1 action.
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DOI：
10.1073/pnas.0902380106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Hoehn, Kyle L.;Salmon, Adam B.;James, David E.
通讯作者：
James, David E.
影响因子：
5.8
作者：
Choi, Jin-Ho;Kang, Minji;Yoo, Han-Wook
通讯作者：
Yoo, Han-Wook
影响因子：
10.5
作者：
Fernández, AM;Kim, JK;Le Roith, D
通讯作者：
Le Roith, D
影响因子：
7.7
作者：
Rueda-Clausen CF;Dolinsky VW;Morton JS;Proctor SD;Dyck JR;Davidge ST
通讯作者：
Davidge ST
影响因子：
4.8
作者：
Shimomura, I;Bashmakov, Y;Horton, JD
通讯作者：
Horton, JD