Relationship between down-regulation of HIC1 and PTEN genes and dysfunction of pancreatic islet cells in diabetic rats.
The aim of the study was to investigate the protein expression of hypermethylated in cancer 1 (HIC1 ) and phosphatase and tensin homologue (PTEN) genes and to study their mRNA expressions in normal and diabetic pancreatic islet cells in rats in order to try and identify the functions of these genes in the development and advancement of diabetes. We further aimed to analyze the expression of mammalian target of rapamycin (mTOR), which is regulated by PTEN and to investigate the possible mechanism of PTEN affecting the function of diabetic islet cells. The expressions of HIC1, PTEN and mTOR genes were examined in the pancreatic islets of 20 normal male Wistar rats and 47 diabetic male Wistar rats by immunohistochemistry, Western blot, RT-PCR and real-time RT-PCR. Results showed that expressions of HIC1 and PTEN in protein and mRNA levels were lower in pancreatic islets of diabetic rats than in normal rats. Expressions of mTOR in protein and mRNA levels were higher in pancreatic islets of diabetic rats than in the normal rats. Marked apoptosis of pancreatic islet cells was observed in 29 cases (29/47, 61.7%) in diabetic rats, but not in the remaining 18 (18/47, 38.3%) diabetic rats. The down-regulation of HIC1 and PTEN and up-regulation of mTOR in protein and mRNA level are positively correlated with functional impairment of islet cells in diabetic rats. From this study we conclude that HIC1, PTEN and mTOR cannot be recognized as the key influencing factors promoting pancreatic islet cells apoptosis of diabetic rats; however, lower expressions of HIC1 and PTEN and higher expression of mTOR may affect the function of the pancreatic islet cells in diabetic rats.
Department of Endocrinology, The First Clinical College of Harbin Medical University, Harbin, PR China.
Hao-ling
HL
Liu
Hai-yan
HY
Yang
Lian-xin
LX
Liu
Yue
Y
Chen
Hong-yu
HY
Kuang
Hui-juan
HJ
Zhang
Hui-qing
HQ
Yin
D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015536:Down-Regulation; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000473:pathology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human