Nutritional programming of pancreatic β-cell plasticity

Abstract

Nutritional insufficiency during pregnancy has been shown to alter the metabolism of the offspring and can increase the risk of type 2 diabetes. The phenotype in the offspring involves changes to the morphology and functional capacity of the endocrine pancreas, and in the supporting islet microvasculature. Pancreatic β-cells possess a plastic potential and can partially recover from catastrophic loss. This is partly due to the existence of progenitors within the islets and the ability to generate new islets by neogenesis from the pancreatic ducts. This regenerative capacity is induced by bone marrow-derived stem cells, including endothelial cell progenitors and is associated with increased angiogenesis within the islets. Nutritional insults in early life, such as feeding a low protein diet to the mother, impair the regenerative capacity of the β-cells. The mechanisms underlying this include a reduced ability of β-cells to differentiate from the progenitor population, changes in the inductive signals from the microvasculature and an altered presence of endothelial progenitors. Statin treatment within animal models was associated with angiogenesis in the islet microvasculature, improved vascular function and an increase in β-cell mass. This demonstrates that reversal of the impaired β-cell phenotype observed following nutritional insult in early life is potentially possible.