Incretin-modulated beta cell energetics in intact islets of Langerhans

Hodson, David J; Tarasov, Andrei I; Gimeno Brias, Silvia; Mitchell, Ryan K; Johnston, Natalie R; Haghollahi, Shahab; Cane, Matthew C; Bugliani, Marco; Marchetti, Piero; Bosco, Domenico; Johnson, Paul R; Hughes, Stephen J; Rutter, Guy A

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Title		Incretin-modulated beta cell energetics in intact islets of Langerhans
Authors		Hodson, David J Tarasov, Andrei I Gimeno Brias, Silvia Mitchell, Ryan K Johnston, Natalie R Haghollahi, Shahab Cane, Matthew C Bugliani, Marco Marchetti, Piero Bosco, Domenico Johnson, Paul R Hughes, Stephen J Rutter, Guy A show all authors [1 - 13]
Published in		Molecular Endocrinology. 2014, vol. 28, no. 6, p. 860-71
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.
Identifiers		DOI: 10.1210/me.2014-1038 PMID: 24766140
Full text		Article (Published version) (1.9 MB) - Free access
Structures		Faculté de médecine / Section de médecine clinique / Département de chirurgie
Research group		Cultures cellulaires et transplantations (519)
Citation (ISO format)		HODSON, David J et al. Incretin-modulated beta cell energetics in intact islets of Langerhans. In: Molecular Endocrinology, 2014, vol. 28, n° 6, p. 860-71. https://archive-ouverte.unige.ch/unige:38915