Journal article
Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail
D Brasacchio, J Okabe, C Tikellis, A Balcerczyk, P George, EK Baker, AC Calkin, M Brownlee, ME Cooper, A El-Osta
Diabetes | AMER DIABETES ASSOC | Published : 2009
DOI: 10.2337/db08-1666
Abstract
OBJECTIVE-Results from the Diabetes Control Complications Trial (DCCT) and the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) Study and more recently from the U.K. Prospective Diabetes Study (UKPDS) have revealed that the deleterious end-organ effects that occurred in both conventional and more aggressively treated subjects continued to operate >5 years after the patients had returned to usual glycemic control and is interpreted as a legacy of past glycemia known as " hyperglycemic memory." We have hypothesized that transient hyperglycemia mediates persistent gene- activating events attributed to changes in epigenetic information. RESEARCH DESIGN AND METHODS-Model..
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Funding Acknowledgements
The authors acknowledge grant support from the Juvenile Diabetes Research Foundation International (JDRF), the Diabetes Australia Research Trust, the National Health and Medical Research Council (NHMRC) of Australia, and the National Heart Foundation of Australia. A.E.-O., M.E.C., and A.C.C. are recipients of a Career Development Award, a Senior Principal Research Fellowship, and a Doherty Post-Doctoral fellowship, respectively, from the NHMRC. C.T. and A.B. are recipients of fellowships from the JDRF and the Foundation for Polish Science.