Pyruvate dehydrogenase activation normalises carbohydrate metabolism and diastolic function in the diabetic heart
Lydia Le Page 1 , Oliver Rider 2 , Andrew Lewis 2 , Lucia Giles 1 , Vicky Ball 1 , Latt Mansor 1 , Lisa Heather 1 , and Damian Tyler 1
Department of Physiology, Anatomy and
Genetics, University of Oxford, Oxford, United Kingdom,
Centre for Clinical Magnetic Resonance Research, Oxford,
Diabetics have reduced systemic glucose metabolism,
partly due to reduced pyruvate dehydrogenase (PDH) flux,
which leads to high blood glucose levels.
Dichloroacetate (DCA) stimulates PDH and this study
on the diabetic heart and liver. Four weeks of DCA
treatment in diabetic rats normalised blood glucose
levels, restored cardiac PDH flux and elevated hepatic
PDH flux compared to controls. Diastolic dysfunction,
observed in the diabetic heart, was not present in
diabetic rats treated with DCA. We conclude that PDH
modulation may be a suitable treatment for the metabolic
and functional abnormalities seen in the diabetic heart.
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