University of Hertfordshire

From the same journal

Incretin-modulated beta cell energetics in intact islets of Langerhans

Research output: Contribution to journalArticlepeer-review

Standard

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.

In: Molecular endocrinology (Baltimore, Md.), Vol. 28, No. 6, 01.06.2014, p. 860-71.

Research output: Contribution to journalArticlepeer-review

Harvard

Hodson, DJ, Tarasov, AI, Gimeno Brias, S, Mitchell, RK, Johnston, NR, Haghollahi, S, Cane, MC, Bugliani, M, Marchetti, P, Bosco, D, Johnson, PR, Hughes, SJ & Rutter, GA 2014, 'Incretin-modulated beta cell energetics in intact islets of Langerhans', Molecular endocrinology (Baltimore, Md.), vol. 28, no. 6, pp. 860-71. https://doi.org/10.1210/me.2014-1038

APA

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 (Baltimore, Md.), 28(6), 860-71. https://doi.org/10.1210/me.2014-1038

Vancouver

Hodson DJ, Tarasov AI, Gimeno Brias S, Mitchell RK, Johnston NR, Haghollahi S et al. Incretin-modulated beta cell energetics in intact islets of Langerhans. Molecular endocrinology (Baltimore, Md.). 2014 Jun 1;28(6):860-71. https://doi.org/10.1210/me.2014-1038

Author

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. / Incretin-modulated beta cell energetics in intact islets of Langerhans. In: Molecular endocrinology (Baltimore, Md.). 2014 ; Vol. 28, No. 6. pp. 860-71.

Bibtex

@article{30b7f2340c244b27893e2486b2a9c753,
title = "Incretin-modulated beta cell energetics in intact islets of Langerhans",
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. ",
keywords = "Adenosine Triphosphate/metabolism, Adult, Animals, Calcium Signaling, Energy Metabolism, Glucagon-Like Peptide 1/physiology, Glucagon-Like Peptide-1 Receptor, Glucose/metabolism, Humans, Incretins/physiology, Insulin-Secreting Cells/metabolism, Membrane Potential, Mitochondrial, Mice, Middle Aged, Receptors, Glucagon/metabolism, Species Specificity, Tissue Culture Techniques",
author = "Hodson, {David J} and Tarasov, {Andrei I} and {Gimeno Brias}, Silvia and Mitchell, {Ryan K} and Johnston, {Natalie R} and Shahab Haghollahi and Cane, {Matthew C} and Marco Bugliani and Piero Marchetti and Domenico Bosco and Johnson, {Paul R} and Hughes, {Stephen J} and Rutter, {Guy A}",
year = "2014",
month = jun,
day = "1",
doi = "10.1210/me.2014-1038",
language = "English",
volume = "28",
pages = "860--71",
journal = "Molecular endocrinology (Baltimore, Md.)",
issn = "0888-8809",
publisher = "The Endocrine Society",
number = "6",

}

RIS

TY - JOUR

T1 - Incretin-modulated beta cell energetics in intact islets of Langerhans

AU - Hodson, David J

AU - Tarasov, Andrei I

AU - Gimeno Brias, Silvia

AU - Mitchell, Ryan K

AU - Johnston, Natalie R

AU - Haghollahi, Shahab

AU - Cane, Matthew C

AU - Bugliani, Marco

AU - Marchetti, Piero

AU - Bosco, Domenico

AU - Johnson, Paul R

AU - Hughes, Stephen J

AU - Rutter, Guy A

PY - 2014/6/1

Y1 - 2014/6/1

N2 - 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.

AB - 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.

KW - Adenosine Triphosphate/metabolism

KW - Adult

KW - Animals

KW - Calcium Signaling

KW - Energy Metabolism

KW - Glucagon-Like Peptide 1/physiology

KW - Glucagon-Like Peptide-1 Receptor

KW - Glucose/metabolism

KW - Humans

KW - Incretins/physiology

KW - Insulin-Secreting Cells/metabolism

KW - Membrane Potential, Mitochondrial

KW - Mice

KW - Middle Aged

KW - Receptors, Glucagon/metabolism

KW - Species Specificity

KW - Tissue Culture Techniques

U2 - 10.1210/me.2014-1038

DO - 10.1210/me.2014-1038

M3 - Article

C2 - 24766140

VL - 28

SP - 860

EP - 871

JO - Molecular endocrinology (Baltimore, Md.)

JF - Molecular endocrinology (Baltimore, Md.)

SN - 0888-8809

IS - 6

ER -