Glucose as an agent of post-translational modification in diabetes--New cardiac epigenetic insights.
Diabetes elicits cardiac metabolic stress involving impaired glucose uptake and metabolic substrate shifts. Diabetic cardiac pathology is well documented in human patients and experimental animal models to be characterized by diastolic dysfunction, but the underlying mechanisms are not well understood. Signaling disturbances involved in cardiac insulin resistance are linked to glucose handling abnormalities. Both reversible (e.g. O-GlcNAc) and irreversible (e.g. AGEs) glucose-modifications of cardiomyocyte extracellular and intracellular proteins are implicated in structural and functional alterations underlying pathology in the diabetic heart. This review highlights some aspects of the epigenetic roles played by glucose (and related hexose sugars) in mediating diabetic cardiac pathology with specific consideration for the mechanisms impinging on post-translational modifications which have key signaling and mechanical impacts.
Department of Physiology, University of Auckland, Auckland, New Zealand.
Kimberley M
KM
Mellor
School of Medical Sciences, University of Auckland, New Zealand.
Margaret A
MA
Brimble
Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia. Electronic address: lmd@unimelb.edu.au.
Lea M D
LM
Delbridge
D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008955:Models, Cardiovascular; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D017127:Glycation End Products, Advanced; D005947:Glucose
Advanced glycation endproducts; Cardiomyocyte; Diabetes; Glycation; Glycosylation; Heart; Insulin resistance; O-GlcNAcylation