Diabetes and obesity during pregnancy alter insulin signalling and glucose transporter expression in maternal skeletal muscle and subcutaneous adipose tissue
Diabetes and obesity during pregnancy alter insulin signalling and glucose transporter expression in maternal skeletal muscle and subcutaneous adipose tissue
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DOI：
10.1677/jme-09-0091
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发表时间：
2010-04-01
影响因子：
3.5
通讯作者：
Lappas, Martha
中科院分区：
文献类型：
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作者：
Colomiere, Michelle;Permezel, Michael;Lappas, Martha
严重的胰岛素抵抗是妊娠期糖尿病(GDM)的重要特征。据推测，胰岛素信号通路的改变和随后的葡萄糖处置是妊娠期糖尿病患者胰岛素抵抗的根本原因。这项研究的目的是为了描述胰岛素信号通路和胰岛素敏感组织中的中间产物。非肥胖组和肥胖组(n=6~8)的皮下脂肪组织和骨骼肌均来自正常糖耐量(NGT)组和胰岛素控制的GDM组。用Western blotting和定量逆转录聚合酶链式反应研究胰岛素信号通路的表达。本研究发现妊娠期糖尿病患者脂肪组织中胰岛素受体底物(IRS)-1、IRS-2、葡萄糖转运蛋白(GLUT)-1、GLUT-4和糖原合成酶-3(GSK)-3亚型基因的mRNA表达水平较正常妊娠妇女明显改变。在骨骼肌中，胰岛素控制的GDM与IRS-1、磷脂酰肌醇-3-激酶(PI3-K)P85α、GLUT-1和-4、GSK-3亚型和磷脂酰肌醇依赖的激酶-1减少相关。GDM患者脂肪组织和骨骼肌中IRS-1和GLUT-4表达降低，PI3-K P85α蛋白表达增加。肥胖女性骨骼肌和脂肪组织中GLUT-1和GLUT-4mRNA表达降低，GLUT-4蛋白表达减弱。总而言之，我们的结果表明，妊娠期糖尿病和肥胖导致脂肪组织和骨骼肌中胰岛素信号转导的缺陷，并可能是妊娠期糖尿病的潜在原因。
Severe insulin resistance is a defining attribute of gestational diabetes mellitus (GDM). It is postulated that alterations in the insulin-signalling pathway and subsequent glucose disposal are the underlying cause of insulin resistance in patients with GDM. The purpose of this study was to profile the insulin-signalling pathway and intermediates in insulin-sensitive tissues. Subcutaneous adipose tissue and skeletal muscle were collected from normal glucose-tolerant (NGT) and insulin-controlled GDM in both non-obese and obese cohorts (n=6-8 per subgroup). Expression studies of the insulin-signalling pathway were performed using western blotting and quantitative reverse transcription-PCR. This study demonstrated altered mRNA expression of insulin receptor substrate (IRS)-1, IRS-2, glucose transporter (GLUT)-1, GLUT-4 and glycogen synthase kinase (GSK)-3 isoforms genes in adipose tissue in GDM women in comparison to NGT pregnant controls. In skeletal muscle, insulin-controlled GDM was associated with decreased IRS-1, phosphatidylinositol-3-kinase (PI3-K) p85 alpha, GLUT-1 and -4, GSK-3 isoforms and phosphoinositide-dependent kinase-1. Both adipose tissue and skeletal muscle from women with GDM displayed decreased IRS-1 and GLUT-4 and increased PI3-K p85 alpha protein expression. Both skeletal muscle and adipose tissue from obese women demonstrated lower GLUT-1 and -4 mRNA expression and diminished GLUT-4 protein expression in skeletal muscle only. Collectively, our results suggest that diabetes and obesity during pregnancy cause defects in insulin-signalling transduction in adipose tissue and skeletal muscle and may be the underlying cause of GDM.