Research article

Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes

Björn Tyrberg¹ , Kamen A Anachkov² , Sergio A Dib³ , Jessica Wang-Rodriguez¹ , Kun-Ho Yoon⁴ and Fred Levine¹

¹UCSD Cancer Center, La Jolla, CA 92037-0912, USA

²Department of Pathology, Sector Anatomic Pathology, Military Medical Academy, Sofia, Bulgaria

³Brazil Division of Endocrinology, Department of Medicine, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil

⁴Kangnam St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea

author email corresponding author email

BMC Endocrine Disorders 2002, 2:2doi:10.1186/1472-6823-2-2

Published:	25 April 2002

Abstract

Background

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.

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 β-cell oxidative metabolism lead to DNA damage and the induction of Ogg1 expression.