Zieleniak Andrzej, Zurawska-Klis Monika, Laszcz Karolina, Bulash Krystsina, Pacyga Dagmara, Cypryk Katarzyna, Wozniak Lucyna, Wojcik Marzena
Department of Structural Biology, Faculty of Biomedical Sciences, Medical University of Lodz, 90-752 Lodz, Poland.
Department of Internal Diseases and Diabetology, Medical University of Lodz, 92-213 Lodz, Poland.
Int J Mol Sci. 2024 Dec 5;25(23):13094. doi: 10.3390/ijms252313094.
Not much is currently known about disturbances in insulin signaling and glucose transport in leukocytes of women with gestational diabetes mellitus (GDM) during and after pregnancy. In this study, the expression of insulin signaling (, , and and glucose transporter (, and )-related genes in the leukocytes of 92 pregnant women was assayed using quantitative RT-PCR. The cohort consisted of 44 women without GDM (NGT group) and 48 with GDM (GDM group) at 24-28 weeks of gestation. GDM women were then tested again one year after childbirth (pGDM group: 14 women (29.2%) with abnormal glucose tolerance (AGT) and 34 women (70.8%) with normoglycemia). The GDM and NGT groups were closely matched for gestational age and parameters of obesity, such as pre-pregnancy body mass index (BMI), pregnancy weight, and gestational weight gain (GWG) ( > 0.05). Compared to the NGT group, the GDM and pGDM groups were hyperglycemic, but the GDM group featured a more highly insulin-resistant condition than the pGDM group, as reflected by higher fasting insulin (FI) levels and the values of the homeostasis model assessment for insulin resistance (HOMA-IR) ( < 0.05). In leukocytes from the GDM and pGDM groups, , , and were upregulated and was downregulated, with a larger magnitude in fold change (FC) values for and in the GDM group and for and in the pGDM group. The expression of was unchanged in the GDM group but upregulated in the pGDM group, where it was inversely correlated with HOMA-IR ( = -0.48; = 0.007). Although the and levels did not significantly differ between the groups, the transcript positively correlated with pregnancy weight, fasting plasma glucose, FI, and HOMA-IR in the GDM group. Our findings indicate that pronounced quantitative changes exist between the GDM and pGDM groups with respect to the expression of certain genes engaged in insulin signaling and glucose transport in leukocytes, with insulin resistance of a variable degree. These data also highlight the relationship of leukocyte expression with insulin resistance in the postpartum period.
目前对于妊娠糖尿病（GDM）女性在孕期及产后白细胞中胰岛素信号传导和葡萄糖转运的紊乱情况了解不多。在本研究中，使用定量逆转录聚合酶链反应（RT-PCR）检测了92名孕妇白细胞中胰岛素信号传导相关基因（胰岛素受体底物1、胰岛素受体底物2、磷脂酰肌醇-3激酶和蛋白激酶B）以及葡萄糖转运蛋白相关基因（葡萄糖转运蛋白1、葡萄糖转运蛋白2和葡萄糖转运蛋白4）的表达。该队列由44名无GDM的女性（正常糖耐量组）和48名妊娠24 - 28周时患有GDM的女性（GDM组）组成。GDM女性在产后一年再次接受检测（产后GDM组：14名女性（29.2%）糖耐量异常（AGT），34名女性（70.8%）血糖正常）。GDM组和正常糖耐量组在孕周以及肥胖参数（如孕前体重指数（BMI）、孕期体重和孕期体重增加（GWG））方面匹配良好（P>0.05）。与正常糖耐量组相比，GDM组和产后GDM组均存在高血糖，但GDM组的胰岛素抵抗状况比产后GDM组更严重，这通过更高的空腹胰岛素（FI）水平和胰岛素抵抗稳态模型评估值（HOMA-IR）得以体现（P<0.05）。在GDM组和产后GDM组的白细胞中，胰岛素受体底物1、胰岛素受体底物2和磷脂酰肌醇-3激酶表达上调，蛋白激酶B表达下调，GDM组中胰岛素受体底物1和磷脂酰肌醇-3激酶的倍数变化（FC）值变化幅度更大，产后GDM组中胰岛素受体底物2和蛋白激酶B的FC值变化幅度更大。葡萄糖转运蛋白1在GDM组中的表达未发生变化，但在产后GDM组中表达上调，且与HOMA-IR呈负相关（r = -0.48；P = 0.007）。尽管各组间葡萄糖转运蛋白2和葡萄糖转运蛋白4的水平无显著差异，但在GDM组中，葡萄糖转运蛋白4转录本与孕期体重、空腹血糖、FI和HOMA-IR呈正相关。我们的研究结果表明，GDM组和产后GDM组在白细胞中参与胰岛素信号传导和葡萄糖转运的某些基因的表达方面存在明显的定量变化，伴有不同程度的胰岛素抵抗。这些数据还突出了产后白细胞葡萄糖转运蛋白4表达与胰岛素抵抗之间的关系。
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