University of Hertfordshire

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Incretin-modulated beta cell energetics in intact islets of Langerhans

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  • David J Hodson
  • Andrei I Tarasov
  • Silvia Gimeno Brias
  • Ryan K Mitchell
  • Natalie R Johnston
  • Shahab Haghollahi
  • Matthew C Cane
  • Marco Bugliani
  • Piero Marchetti
  • Domenico Bosco
  • Paul R Johnson
  • Stephen J Hughes
  • Guy A Rutter
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Original languageEnglish
Pages (from-to)860-71
Number of pages12
JournalMolecular endocrinology (Baltimore, Md.)
Early online date25 Apr 2014
Publication statusPublished - 1 Jun 2014


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.

ID: 15267161