Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes
<p>Abstract</p> <p>Background</p> <p>It has become increasingly clear that β-cell failure plays a critical role in the pathogenesis of type 2 diabetes. Free-radical mediated β-cell damage has been intensively studied in type 1 diabetes, but not in human type 2 diabetes....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2002-04-01
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| Series: | BMC Endocrine Disorders |
| Online Access: | http://www.biomedcentral.com/1472-6823/2/2 |
| _version_ | 1811296983538728960 |
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| author | Yoon Kun-Ho Wang-Rodriguez Jessica Dib Sergio A Anachkov Kamen A Tyrberg Björn Levine Fred |
| author_facet | Yoon Kun-Ho Wang-Rodriguez Jessica Dib Sergio A Anachkov Kamen A Tyrberg Björn Levine Fred |
| author_sort | Yoon Kun-Ho |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>It has become increasingly clear that β-cell failure plays a critical role in the pathogenesis of type 2 diabetes. Free-radical mediated β-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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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 β-cell oxidative metabolism lead to DNA damage and the induction of Ogg1 expression.</p> |
| first_indexed | 2024-04-13T05:56:27Z |
| format | Article |
| id | doaj.art-0b0b5cac130e45468bae4d22f245b60a |
| institution | Directory Open Access Journal |
| issn | 1472-6823 |
| language | English |
| last_indexed | 2024-04-13T05:56:27Z |
| publishDate | 2002-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Endocrine Disorders |
| spelling | doaj.art-0b0b5cac130e45468bae4d22f245b60a2022-12-22T02:59:36ZengBMCBMC Endocrine Disorders1472-68232002-04-0121210.1186/1472-6823-2-2Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetesYoon Kun-HoWang-Rodriguez JessicaDib Sergio AAnachkov Kamen ATyrberg BjörnLevine Fred<p>Abstract</p> <p>Background</p> <p>It has become increasingly clear that β-cell failure plays a critical role in the pathogenesis of type 2 diabetes. Free-radical mediated β-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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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 β-cell oxidative metabolism lead to DNA damage and the induction of Ogg1 expression.</p>http://www.biomedcentral.com/1472-6823/2/2 |
| spellingShingle | Yoon Kun-Ho Wang-Rodriguez Jessica Dib Sergio A Anachkov Kamen A Tyrberg Björn Levine Fred Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes BMC Endocrine Disorders |
| title | Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes |
| title_full | Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes |
| title_fullStr | Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes |
| title_full_unstemmed | Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes |
| title_short | Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes |
| title_sort | islet expression of the dna repair enzyme 8 oxoguanosine dna glycosylase ogg1 in human type 2 diabetes |
| url | http://www.biomedcentral.com/1472-6823/2/2 |
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