الفهرس 
DIABETES MELLITUS
Complications of DiabetesOnly 14 pages are availabe for public view
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Abstract
Over recent decades, diabetes mellitus has become one of the major healthcare problems worldwide (Zang et al., 2017).Cardiovascular disease is a major cause of mortality in diabetes mellitus type 1 (T1DM) (Lee et al., 2015).
Recent studies have started to unveil an unexpected and powerful role of microRNAs in numerous forms of diseases (Zampetaki et al., 2016). miRNAs play a remarkable role in the pathogenesis of diabetes mellitus type 1 and its associated cardiovascular complications by regulating multiple genes expression (Chavali et al., 2014).
MiR-133a is the most abundant microRNAs in the heart and has been reported to regulate cardiac ion channels (Hedley et al., 2014). Several studies have demonstrated the crucial role of miR-133 in different cardiovascular diseases (Rawal et al., 2014). It was also found that miR-133a, induced by hyperglycemia, leads to beta-cell dysfunction and suppression of insulin biosynthesis (Fred et al., 2010).
Mesenchymal stem cells have been envisioned as a promising tool for T1D treatment few years ago (Ezquer et al., 2014).
This study was carried out at Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University (2016-2018) in collaboration with physiology department, Faculty of Medicine, Ain Shams University and the biochemistry &molecular biology unit -Cairo University. The study was approved by Research Ethics Committee (REC), Faculty of Medicine, Ain Shams University.
The aim of this study is to evaluate the expression of miRNA-133a in pancreatic and cardiac tissues of diabetic rats with cardiovascular complications before and after treatment with mesenchymal stem cells.
This study included twenty four adult male Wistar rats that were equally divided into three groups (n=8/ each group):
1. group 1 (control): injected once with 0.05 M citrate buffer, intra-peritoneal (IP).
2. group 2 (STZ): injected IP once with 35 mg/kg body weight streptozotocin (STZ) dissolved in 0.05 M citrate buffer.
3. group 3 (STZ/MSCs): injected IP once with 35 mg/kg body weight streptozotocin (STZ) dissolved in 0.05 M citrate buffer, followed by IV (intravenous) injection of single dose of labeled BM-MSCs with PKH-26 red fluorescent dye at a dose of 3x106 cells at rat tail. All rats were sacrificed eight weeks after the start of the study.
All groups were subjected to:
Measurement of random blood glucose level in rat tail blood 3 days after induction of diabetes to confirm being diabetic. The measurement was repeated every 2 weeks throughout the study duration.
Measurement of arterial blood pressure, and recording of ECG for each rat at 2 weeks interval. Measurement of fasting blood glucose (FBG), and fasting serum insulin using an ELISA kit.
Excision of pancreatic and cardiac tissues for miRNA extraction, reverse transcription and quantification of miR-133a expression by real time PCR.
Confirmation of homing of fluorescent labeled BM-MSCs using fluorescent microscope to cardiac and pancreatic tissues of group three rats.
Histo-pathological examination of H&E stained cardiac and pancreatic tissues from rats in the three groups (using light microscope).
The results of the current study revealed the following:
In diabetic rats, the body weight, fasting blood glucose and serum insulin were significantly changed, also the blood pressure was elevated and QTc interval was prolonged. Furthermore, miR-133a expression was significantly increased in pancreatic and cardiac tissues and positively correlated with FBG concentration.
Mesenchymal stem cells were able to home in the diseased pancreatic and cardiac tissues in diabetic rats as detected by fluorescence microscope, and resulted in improvement of pancreatic and cardiac tissue architecture as revealed by histo-pathological examination.
Diabetic rats treated with MSCs showed significant improvement in body weight, serum insulin levels, but fasting blood glucose didn’t reach the euglycemic concentration. The cardiovascular performance was also improved as revealed by significant decrease in blood pressure and lowered QTc interval. Meanwhile, the expression of miR-133a was decreased but didn’t reach the level of expression in the control group.