Gestational diabetes leads to down-regulation of CDK۴-pRB-E۲F۱ pathway genes in pancreatic islets of rat offspring
- سال انتشار: 1396
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 20، شماره: 2
- کد COI اختصاصی: JR_IJBMS-20-2_007
- زبان مقاله: انگلیسی
- تعداد مشاهده: 231
نویسندگان
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
Stem Cell Research Center, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
Gorgan Congenital Malformations Research Center, Depatment of Anatomical Sciences, Golestan University of Medical Sciences, Gorgan, Iran
چکیده
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 ۱ and type ۲ diabetes). Some recent studies have provided evidence that the CDK۴-pRB-E۲F۱ regulatory pathway is involved in β-cells proliferation. Therefore, we postulated that GDM exposure impacts the offspring’s β-cells by disruption in the CDK۴-pRB-E۲F۱ pathway. Materials and Methods: Adult Wistar rats were randomly allocated in control and diabetic group. The experimental group received ۴۰ 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 ۱۵ 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 ۶.۲ and CDK۴-pRB-E۲F۱ pathway genes by quantitative real-time PCR. Results: GDM reduced the expression of CDK۴-pRB-E۲F۱ pathway genes in Langerhans islets cells of offspring. CDK۴, pRB and E۲F۱ pathway genes were downregulated in diabetic islets by ۵۱%, ۳۵% and ۸۴%, respectively. Also, the expression of Kir ۶.۲ was significantly decreased in diabetic islets by ۸۸%. Conclusion: We suggest that the effect of gestational diabetes on offspring’s β-cells may be primarily caused by the suppression of CDK۴-pRB-E۲F۱ pathway.کلیدواژه ها
Gene expression, Gestational Diabetes Mellitus, Langerhans islets, Offspringاطلاعات بیشتر در مورد COI
COI مخفف عبارت CIVILICA Object Identifier به معنی شناسه سیویلیکا برای اسناد است. COI کدی است که مطابق محل انتشار، به مقالات کنفرانسها و ژورنالهای داخل کشور به هنگام نمایه سازی بر روی پایگاه استنادی سیویلیکا اختصاص می یابد.
کد COI به مفهوم کد ملی اسناد نمایه شده در سیویلیکا است و کدی یکتا و ثابت است و به همین دلیل همواره قابلیت استناد و پیگیری دارد.