Gestational diabetes leads to down-regulation of CDK4-pRB-E2F1 pathway genes in pancreatic islets of rat offspring

Nazari, Zahra and Nabiuni, Mohammad and Saeidi, Mohsen and Golalipour, Mohammad Jafar (2017) Gestational diabetes leads to down-regulation of CDK4-pRB-E2F1 pathway genes in pancreatic islets of rat offspring. Iranian Journal of Basic Medical Sciences, 20 (2). pp. 150-154.

IJBMS_Volume 20_Issue 2_Pages 150-154.pdf

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Objective(s): 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

Item Type: Article
Subjects: QZ pathology-Neoplasms
Divisions: Journals > Iranian J Basic Medical Sciences
Depositing User: ijbms ijbms
Date Deposited: 24 Sep 2017 14:28
Last Modified: 24 Sep 2017 14:28

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