dc.contributor.author | Hodson, David J | |
dc.contributor.author | Tarasov, Andrei I | |
dc.contributor.author | Gimeno Brias, Silvia | |
dc.contributor.author | Mitchell, Ryan K | |
dc.contributor.author | Johnston, Natalie R | |
dc.contributor.author | Haghollahi, Shahab | |
dc.contributor.author | Cane, Matthew C | |
dc.contributor.author | Bugliani, Marco | |
dc.contributor.author | Marchetti, Piero | |
dc.contributor.author | Bosco, Domenico | |
dc.contributor.author | Johnson, Paul R | |
dc.contributor.author | Hughes, Stephen J | |
dc.contributor.author | Rutter, Guy A | |
dc.date.accessioned | 2018-09-05T00:12:43Z | |
dc.date.available | 2018-09-05T00:12:43Z | |
dc.date.issued | 2014-06-01 | |
dc.identifier.citation | Hodson , D J , Tarasov , A I , Gimeno Brias , S , Mitchell , R K , Johnston , N R , Haghollahi , S , Cane , M C , Bugliani , M , Marchetti , P , Bosco , D , Johnson , P R , Hughes , S J & Rutter , G A 2014 , ' Incretin-modulated beta cell energetics in intact islets of Langerhans ' , Molecular Endocrinology , vol. 28 , no. 6 , pp. 860-71 . https://doi.org/10.1210/me.2014-1038 | |
dc.identifier.issn | 0888-8809 | |
dc.identifier.other | PubMedCentral: PMC4042069 | |
dc.identifier.other | ORCID: /0000-0002-8883-176X/work/62751477 | |
dc.identifier.uri | http://hdl.handle.net/2299/20515 | |
dc.description.abstract | Incretins such as glucagon-like peptide 1 (GLP-1) are released from the gut and potentiate insulin release in a glucose-dependent manner. Although this action is generally believed to hinge on cAMP and protein kinase A signaling, up-regulated beta cell intermediary metabolism may also play a role in incretin-stimulated insulin secretion. By employing recombinant probes to image ATP dynamically in situ within intact mouse and human islets, we sought to clarify the role of GLP-1-modulated energetics in beta cell function. Using these techniques, we show that GLP-1 engages a metabolically coupled subnetwork of beta cells to increase cytosolic ATP levels, an action independent of prevailing energy status. We further demonstrate that the effects of GLP-1 are accompanied by alterations in the mitochondrial inner membrane potential and, at elevated glucose concentration, depend upon GLP-1 receptor-directed calcium influx through voltage-dependent calcium channels. Lastly, and highlighting critical species differences, beta cells within mouse but not human islets respond coordinately to incretin stimulation. Together, these findings suggest that GLP-1 alters beta cell intermediary metabolism to influence ATP dynamics in a species-specific manner, and this may contribute to divergent regulation of the incretin-axis in rodents and man. | en |
dc.format.extent | 12 | |
dc.format.extent | 1969389 | |
dc.language.iso | eng | |
dc.relation.ispartof | Molecular Endocrinology | |
dc.subject | Adenosine Triphosphate/metabolism | |
dc.subject | Adult | |
dc.subject | Animals | |
dc.subject | Calcium Signaling | |
dc.subject | Energy Metabolism | |
dc.subject | Glucagon-Like Peptide 1/physiology | |
dc.subject | Glucagon-Like Peptide-1 Receptor | |
dc.subject | Glucose/metabolism | |
dc.subject | Humans | |
dc.subject | Incretins/physiology | |
dc.subject | Insulin-Secreting Cells/metabolism | |
dc.subject | Membrane Potential, Mitochondrial | |
dc.subject | Mice | |
dc.subject | Middle Aged | |
dc.subject | Receptors, Glucagon/metabolism | |
dc.subject | Species Specificity | |
dc.subject | Tissue Culture Techniques | |
dc.title | Incretin-modulated beta cell energetics in intact islets of Langerhans | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Department of Biological and Environmental Sciences | |
dc.contributor.institution | Biosciences Research Group | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1210/me.2014-1038 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |