Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight - potential link to increased risk of diabetes?
Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight - potential link to increased risk of diabetes?
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DOI：
10.1007/s00125-006-0466-2
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发表时间：
2006-12-01
期刊：
影响因子：
8.2
通讯作者：
Vaag, A. A.
中科院分区：
文献类型：
--
作者：
Ozanne, S. E.;Jensen, C. B.;Vaag, A. A.
目的/假设低出生体重的个体患2型糖尿病的风险增加。然而，潜在的分子机制尚不清楚。之前我们已经证明，低出生体重与肌肉胰岛素信号蛋白的变化有关。在这里，我们确定低出生体重是否与脂肪组织中胰岛素信号蛋白的变化有关。方法从丹麦医学出生登记处招募出生体重低（最低10百分位）（n = 17）或正常（第50 -90百分位）（n = 17）的男性（23岁），并进行皮下脂肪活检。结果两组患者胰岛素受体、蛋白激酶C - zeta、糖原合成酶激酶3 (GSK3) α、GSK3 β、蛋白激酶B α和β、过氧化物酶体增殖激活受体γ辅助激活因子1和含src -同源-2蛋白的蛋白水平均无差异。然而，低出生体重男性的GLUT4（也被称为溶质载体家族2[促进葡萄糖转运体]，成员4 [SLC2A4]）的水平（52 +/- 10.9%,p < 0.01），磷酸肌肽3激酶（PI3K）的p85 α亚基（45 +/- 9%,p < 0.01）， PI3K的p110 β亚基（48 +/- 17%,p = 0.06）和IRS1 （59 +/- 24%, p < 0.05）的水平降低。结论/解释这些发现表明，低出生体重与脂肪胰岛素信号蛋白水平降低有关，因此提供了一个潜在的分子框架来解释为什么低出生体重的人患2型糖尿病的风险增加。这些差异先于糖尿病的发展，因此可能有助于预测疾病风险。
Aims/hypothesis Individuals with low birthweight are at increased risk of type 2 diabetes mellitus. However, the underlying molecular mechanisms are unknown. Previously we have shown that low birthweight is associated with changes in muscle insulin signalling proteins. Here we determined whether low birthweight is associated with changes in insulin signalling proteins in adipose tissue.Methods Men (age 23 years) with either a low (bottom 10th percentile) (n = 17) or a normal (50th-90th percentile) (n = 17) birthweight were recruited from the Danish Medical Birth Registry and subcutaneous adipose biopsies were taken.Results Between the two groups there was no difference in protein level of the insulin receptor, protein kinase C zeta, glycogen synthase kinase-3 (GSK3) alpha, GSK3 beta, protein kinase B alpha and beta, peroxisome proliferative activated receptor gamma coactivator 1 or Src-homology-2-containing protein. However, the levels of GLUT4 (also known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) (52 +/- 10.9% reduction, p < 0.01), p85 alpha subunit of phosphoinositide 3-kinase (PI3K) (45 +/- 9% reduction, p < 0.01), p110 beta subunit of PI3K (48 +/- 17% reduction, p = 0.06) and IRS1 (59 +/- 24% reduction, p < 0.05) were reduced in men of low birthweight.Conclusions/interpretation These findings show that low birthweight is associated with reduced levels of adipose insulin signalling proteins, thus providing a potential molecular framework to explain why people with low birthweight are at increased risk of developing type 2 diabetes. These differences precede the development of diabetes and thus may help predict disease risk.