Journal Article


P Maechler
L Brennan
P Newsholme
K Bender



oxidation reduction insulin secreting cells glucose malates insulin cytosol animals malic acid metabolism alpha glycerophosphoric acid aspartic acid glycerophosphates secretion mitochondria energy metabolism flavin adenine dinucleotide nad physiology models biological

The importance of redox shuttles to pancreatic beta-cell energy metabolism and function. (2006)

Abstract The coupling of cytosolic glycolytic NADH production with the mitochondrial electron transport chain is crucial for pancreatic beta-cell function and energy metabolism. The activity of lactate dehydrogenase in the beta-cell is low, thus glycolysis-derived electrons are transported towards the mitochondrial matrix by a NADH shuttle system, which in turn regenerates cytosolic NAD+. Mitochondrial electron transport then produces ATP, the main coupling factor for insulin secretion. Aralar1, a Ca2+-sensitive member of the malate-aspartate shuttle expressed in beta-cells, has been found to play a significant role in nutrient-stimulated insulin secretion and beta-cell function. Increased capacity of Aralar1 enhances the responsiveness of the cell to glucose. Conversely, inhibition of the malate-aspartate shuttle results in impaired glucose metabolism and insulin secretion. Current research investigates potentiating or attenuating activities of various amino acids on insulin secretion, mitochondrial membrane potential and NADH production in Aralar1-overexpressing beta-cells. This work may provide evidence for a central role of Aralar1 in the regulation of nutrient metabolism in the beta-cells.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

P Maechler, L Brennan, P Newsholme, K Bender

Experts in our system

Lorraine Brennan
University College Dublin
Total Publications: 166
Philip Newsholme
University College Dublin
Total Publications: 51