Pyruvate Oxidation Is Critical Determinant of Pancreatic Islet Number and Beta-Cell Mass

Researchers at the University at Buffalo, led by Dr. Mulchand Patel and also at Lawson Health Research Institute and Western Ontario, London, Canada, led by Dr. David Hill, collaboratively evaluated the role of the mitochondrial multienzyme pyruvate dehydrogenase complex in the regulation of pancreatic beta-cell development and maturation in the immediate postnatal period in mice. This study, reported in the August 2014 issue of Experimental Biology and Medicine, demonstrated that the pyruvate dehydrogenase complex is not only required for insulin gene expression and glucose-stimulated insulin secretion, but also directly influences beta-cell (see image) growth and maturity. This places glucose metabolism as a direct regulator of beta-cell mass and plasticity. Glucose metabolism within the pancreatic beta-cells is crucial for insulin gene expression and hormone exocytosis, but there is increasing evidence that glucose metabolic pathways are also important for beta-cell development and the maintenance of beta-cell mass in adult life. A targeted deletion of glucokinase in mouse beta-cells not only prevents glucose-stimulated insulin secretion, but also prevents beta-cell proliferation and is associated with increased apoptosis. A direct manipulation of glucose availability to the embryonic pancreas in tissue culture showed that it was necessary for both alpha- and beta-cell development through the regulation of the transcription factors Neurogenin 3 (Neurog3) and NeuroD.
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