Nazari Zahra, Nabiuni Mohammad, Saeidi Mohsen, Golalipour Mohammad Jafar
Department of Animal Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Iran J Basic Med Sci. 2017 Feb;20(2):150-154. doi: 10.22038/ijbms.2017.8240.
The link between a hyperglycemic intrauterine environment and the development of diabetes later in life has been observed in offspring exposed to gestational diabetes mellitus (GDM), but the underlying mechanisms for this phenomenon are still not clear. Reduced β-cells mass is a determinant in the development of diabetes (type 1 and type 2 diabetes). Some recent studies have provided evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in β-cells proliferation. Therefore, we postulated that GDM exposure impacts the offspring's β-cells by disruption in the CDK4-pRB-E2F1 pathway.
Adult Wistar rats were randomly allocated in control and diabetic group. The experimental group received 40 mg/kg/body weight of streptozotocin (STZ) on day zero of gestation. After delivery, diabetic offspring of GDM mothers and control dams at the age of 15 week were randomly scarified and pancreases were harvested. Langerhans islets of diabetic and control groups were digested by collagenase digestion technique. After RNA extraction, we investigated the expressions of the kir 6.2 and CDK4-pRB-E2F1 pathway genes by quantitative real-time PCR.
GDM reduced the expression of CDK4-pRB-E2F1 pathway genes in Langerhans islets cells of offspring. CDK4, pRB and E2F1 pathway genes were downregulated in diabetic islets by 51%, 35% and 84%, respectively. Also, the expression of Kir 6.2 was significantly decreased in diabetic islets by 88%.
We suggest that the effect of gestational diabetes on offspring's β-cells may be primarily caused by the suppression of CDK4-pRB-E2F1 pathway.
在暴露于妊娠期糖尿病（GDM）的后代中，已观察到高血糖宫内环境与日后患糖尿病之间的联系，但这种现象的潜在机制仍不清楚。β细胞数量减少是糖尿病（1型和2型糖尿病）发生发展的一个决定因素。最近的一些研究提供了证据表明CDK4-pRB-E2F1调节通路参与β细胞增殖。因此，我们推测GDM暴露通过破坏CDK4-pRB-E2F1通路影响后代的β细胞。
成年Wistar大鼠随机分为对照组和糖尿病组。实验组在妊娠第0天接受40mg/kg体重的链脲佐菌素（STZ）。分娩后，在15周龄时随机处死GDM母亲的糖尿病后代和对照组母鼠的后代，并采集胰腺。采用胶原酶消化技术消化糖尿病组和对照组的胰岛。提取RNA后，通过定量实时PCR研究kir 6.2和CDK4-pRB-E2F1通路基因的表达。
GDM降低了后代胰岛细胞中CDK4-pRB-E2F1通路基因的表达。糖尿病胰岛中CDK4、pRB和E2F1通路基因分别下调了51%、35%和84%。此外，糖尿病胰岛中Kir 6.2的表达显著降低了88%。
我们认为妊娠期糖尿病对后代β细胞的影响可能主要是由CDK4-pRB-E2F1通路的抑制引起的。
