Journal article

Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia

Assam El-Osta, Daniella Brasacchio, Dachun Yao, Alessandro Pocai, Peter L Jones, Robert G Roeder, Mark E Cooper, Michael Brownlee

JOURNAL OF EXPERIMENTAL MEDICINE | ROCKEFELLER UNIV PRESS | Published : 2008

Abstract

The current goal of diabetes therapy is to reduce time-averaged mean levels of glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c only explains <25% of the variation in risk of developing complications. Because HbA1c does not correlate with glycemic variability when adjusted for mean blood glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c-independent risk factor for diabetic complications. We show that transient hyperglycemia induces long-lasting activating epigenetic changes in the promoter of the nuclear factor kappaB (NF-kappaB) subunit p65 in aortic endothelial cells both in vitro and in nondiabetic mice, which cause increased p65..

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University of Melbourne Researchers

Grants

Awarded by NIDDK


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

This study was funded by a Center Grant from the Juvenile Diabetes Research Foundation (M. Brownlee, D. Yao, and M. E. Cooper), a JDRF Scholar Award (M. Brownlee), NIDDK grant DK060764 (R. G. Roeder), and grants from the National Health and Medical Research Council of Australia, National Heart Foundation of Australia, and Juvenile Diabetes Research Foundation (A. El-Osta and M. E. Cooper).