Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND: It has become increasingly clear that beta-cell failure plays a critical role in the pathogenesis of type 2 diabetes. Free-radical mediated beta-cell damage has been intensively studied in type 1 diabetes, but not in human type 2 diabetes. Therefore, we studied the protein expression of the DNA repair enzyme Ogg1 in pancreases from type 2 diabetics. Ogg1 was studied because it is the major enzyme involved in repairing 7,8-dihydro-8-oxoguanosine DNA adducts, a lesion previously observed in a rat model of type 2 diabetes. Moreover, in a gene expression screen, Ogg1 was over-expressed in islets from a human type 2 diabetic. METHODS: Immunofluorescent staining of Ogg1 was performed on pancreatic specimens from healthy controls and patients with diabetes for 2-23 years. The intensity and islet area stained for Ogg1 was evaluated by semi-quantitative scoring. RESULTS: Both the intensity and the area of islet Ogg1 staining were significantly increased in islets from the type 2 diabetic subjects compared to the healthy controls. A correlation between increased Ogg1 fluorescent staining intensity and duration of diabetes was also found. Most of the staining observed was cytoplasmic, suggesting that mitochondrial Ogg1 accounts primarily for the increased Ogg1 expression. CONCLUSION: We conclude that oxidative stress related DNA damage may be a novel important factor in the pathogenesis of human type 2 diabetes. An increase of Ogg1 in islet cell mitochondria is consistent with a model in which hyperglycemia and consequent increased beta-cell oxidative metabolism lead to DNA damage and the induction of Ogg1 expression.
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PMID:Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes. 1200 41

This study was aimed to construct the recombinant adenovirus containing rat insulin-like growth factor 1(rIGF-1), and then to investigate its expression in islet beta-cells. RNA was extracted using Trizol from rat livers. rIGF-1 cDNA was obtained using RT-PCR. The purified RT-PCR products and pAdTrack-CMV were digested using Bg1 II and EcoR V and religated by T4 DNA ligase, then transformed into electro-competent JM109 bacteria and selected on Kanamycin LB plates. This plasmid pAd-CMV-rIGF-1 was linearized by PmeI and co-transformed into electro-competent BJ5183 bacteria with pAdEasy-1 and selected on Kanamycin LB plates. After having been screened, the extracted plasmid of positive bacteria was transfected into HEK 293 cells with liposome and was identified by the green fluorescence protein (GFP) expression. The recombinant adenovirus encoding rIGF-1 was named Ad-rIGF-1, and the viral particles were further amplified, purified, and its titer was about 4.0 x 10(8)pfu/ml. Ad-rIGF-1 was transfected into rat pancreatic beta cell lines- RINm5F cells, RT-PCR was carried out to detect the transfer genes, rIGF-1 protein in cells culture supernatants was detected by ELISA method, and its concentration was 91.6 +/- 26.8 ng/ml. rIGF-1 was present in Ad-rIGF-1-infected RINm5F cells as measured by Western blotting. The recombinant adenovirus vector containing rIGF-1 was constructed successfully, and the rIGF-1 protein was expressed by RINm5F cells. This method provided the mechanism of rLGF-1 to prevent beta cell from impairmentand to treat the case of type 1 diabetes.
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PMID:[Construction of recombinant adenovirus vector containing rat insulin-like growth factor 1 gene and its expression in islet beta-cells]. 1994 92