title: Gestational diabetes leads to down-regulation of CDK4-pRB-E2F1 pathway genes in pancreatic islets of rat offspring.
abstract: OBJECTIVE
  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.
  
  
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Animal Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Nazari
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Nabiuni
authors.affiliation: Stem Cell Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Saeidi
authors.affiliation: Gorgan Congenital Malformations Research Center, Depatment of Anatomical Sciences, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Mohammad Jafar
authors.initials: MJ
authors.lastname: Golalipour
keywords: Gene expression; Gestational diabetes – mellitus; Langerhans islets; Offspring