Neuronatin regulates pancreatic β cell insulin content and secretion

Research output: Contribution to journalArticlepeer-review

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Neuronatin regulates pancreatic β cell insulin content and secretion. / Millership, Steven J; da Silva Xavier, Gabriela; Choudhury, Agharul I; Bertazzo, Sergio; Chabosseau, Pauline; Pedroni, Silvia Ma; Irvine, Elaine E; Montoya, Alex; Faull, Peter; Taylor, William R; Kerr-Conte, Julie; Pattou, Francois; Ferrer, Jorge; Christian, Mark; John, Rosalind M; Latreille, Mathieu; Liu, Ming; Rutter, Guy A; Scott, James; Withers, Dominic J.

In: Journal of Clinical Investigation, Vol. 128, No. 8, 01.08.2018, p. 3369–3381.

Research output: Contribution to journalArticlepeer-review

Harvard

Millership, SJ, da Silva Xavier, G, Choudhury, AI, Bertazzo, S, Chabosseau, P, Pedroni, SM, Irvine, EE, Montoya, A, Faull, P, Taylor, WR, Kerr-Conte, J, Pattou, F, Ferrer, J, Christian, M, John, RM, Latreille, M, Liu, M, Rutter, GA, Scott, J & Withers, DJ 2018, 'Neuronatin regulates pancreatic β cell insulin content and secretion', Journal of Clinical Investigation, vol. 128, no. 8, pp. 3369–3381. https://doi.org/10.1172/JCI120115

APA

Millership, S. J., da Silva Xavier, G., Choudhury, A. I., Bertazzo, S., Chabosseau, P., Pedroni, S. M., Irvine, E. E., Montoya, A., Faull, P., Taylor, W. R., Kerr-Conte, J., Pattou, F., Ferrer, J., Christian, M., John, R. M., Latreille, M., Liu, M., Rutter, G. A., Scott, J., & Withers, D. J. (2018). Neuronatin regulates pancreatic β cell insulin content and secretion. Journal of Clinical Investigation, 128(8), 3369–3381. https://doi.org/10.1172/JCI120115

Vancouver

Millership SJ, da Silva Xavier G, Choudhury AI, Bertazzo S, Chabosseau P, Pedroni SM et al. Neuronatin regulates pancreatic β cell insulin content and secretion. Journal of Clinical Investigation. 2018 Aug 1;128(8):3369–3381. https://doi.org/10.1172/JCI120115

Author

Millership, Steven J ; da Silva Xavier, Gabriela ; Choudhury, Agharul I ; Bertazzo, Sergio ; Chabosseau, Pauline ; Pedroni, Silvia Ma ; Irvine, Elaine E ; Montoya, Alex ; Faull, Peter ; Taylor, William R ; Kerr-Conte, Julie ; Pattou, Francois ; Ferrer, Jorge ; Christian, Mark ; John, Rosalind M ; Latreille, Mathieu ; Liu, Ming ; Rutter, Guy A ; Scott, James ; Withers, Dominic J. / Neuronatin regulates pancreatic β cell insulin content and secretion. In: Journal of Clinical Investigation. 2018 ; Vol. 128, No. 8. pp. 3369–3381.

Bibtex

@article{1c1f49ebfc1b4091865c6546aa0c6e9a,
title = "Neuronatin regulates pancreatic β cell insulin content and secretion",
abstract = "Neuronatin (Nnat) is an imprinted gene implicated in human obesity and widely expressed in neuroendocrine and metabolic tissues in a hormone and nutrient-sensitive manner. However, its molecular and cellular functions and precise role in organismal physiology remain only partly defined. Here we demonstrate that mice lacking Nnat globally or specifically in β cells display impaired glucose-stimulated insulin secretion leading to defective glucose handling under conditions of nutrient-excess. In contrast, we report no evidence for any feeding or body weight phenotypes in global Nnat null mice. At the molecular level neuronatin augments insulin signal peptide cleavage by binding to the signal peptidase complex and facilitates translocation of the nascent preprohormone. Loss of neuronatin expression in β cells therefore reduces insulin content and blunts glucose-stimulated insulin secretion. Nnat expression, in turn, is glucose-regulated. This mechanism therefore represents a novel site of nutrient-sensitive control of β cell function and whole animal glucose homeostasis. These data also suggest a potential wider role for Nnat in the regulation of metabolism through the modulation of peptide processing events.",
author = "Millership, {Steven J} and {da Silva Xavier}, Gabriela and Choudhury, {Agharul I} and Sergio Bertazzo and Pauline Chabosseau and Pedroni, {Silvia Ma} and Irvine, {Elaine E} and Alex Montoya and Peter Faull and Taylor, {William R} and Julie Kerr-Conte and Francois Pattou and Jorge Ferrer and Mark Christian and John, {Rosalind M} and Mathieu Latreille and Ming Liu and Rutter, {Guy A} and James Scott and Withers, {Dominic J}",
year = "2018",
month = aug,
day = "1",
doi = "10.1172/JCI120115",
language = "English",
volume = "128",
pages = "3369–3381",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "8",

}

RIS

TY - JOUR

T1 - Neuronatin regulates pancreatic β cell insulin content and secretion

AU - Millership, Steven J

AU - da Silva Xavier, Gabriela

AU - Choudhury, Agharul I

AU - Bertazzo, Sergio

AU - Chabosseau, Pauline

AU - Pedroni, Silvia Ma

AU - Irvine, Elaine E

AU - Montoya, Alex

AU - Faull, Peter

AU - Taylor, William R

AU - Kerr-Conte, Julie

AU - Pattou, Francois

AU - Ferrer, Jorge

AU - Christian, Mark

AU - John, Rosalind M

AU - Latreille, Mathieu

AU - Liu, Ming

AU - Rutter, Guy A

AU - Scott, James

AU - Withers, Dominic J

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Neuronatin (Nnat) is an imprinted gene implicated in human obesity and widely expressed in neuroendocrine and metabolic tissues in a hormone and nutrient-sensitive manner. However, its molecular and cellular functions and precise role in organismal physiology remain only partly defined. Here we demonstrate that mice lacking Nnat globally or specifically in β cells display impaired glucose-stimulated insulin secretion leading to defective glucose handling under conditions of nutrient-excess. In contrast, we report no evidence for any feeding or body weight phenotypes in global Nnat null mice. At the molecular level neuronatin augments insulin signal peptide cleavage by binding to the signal peptidase complex and facilitates translocation of the nascent preprohormone. Loss of neuronatin expression in β cells therefore reduces insulin content and blunts glucose-stimulated insulin secretion. Nnat expression, in turn, is glucose-regulated. This mechanism therefore represents a novel site of nutrient-sensitive control of β cell function and whole animal glucose homeostasis. These data also suggest a potential wider role for Nnat in the regulation of metabolism through the modulation of peptide processing events.

AB - Neuronatin (Nnat) is an imprinted gene implicated in human obesity and widely expressed in neuroendocrine and metabolic tissues in a hormone and nutrient-sensitive manner. However, its molecular and cellular functions and precise role in organismal physiology remain only partly defined. Here we demonstrate that mice lacking Nnat globally or specifically in β cells display impaired glucose-stimulated insulin secretion leading to defective glucose handling under conditions of nutrient-excess. In contrast, we report no evidence for any feeding or body weight phenotypes in global Nnat null mice. At the molecular level neuronatin augments insulin signal peptide cleavage by binding to the signal peptidase complex and facilitates translocation of the nascent preprohormone. Loss of neuronatin expression in β cells therefore reduces insulin content and blunts glucose-stimulated insulin secretion. Nnat expression, in turn, is glucose-regulated. This mechanism therefore represents a novel site of nutrient-sensitive control of β cell function and whole animal glucose homeostasis. These data also suggest a potential wider role for Nnat in the regulation of metabolism through the modulation of peptide processing events.

U2 - 10.1172/JCI120115

DO - 10.1172/JCI120115

M3 - Article

C2 - 29864031

VL - 128

SP - 3369

EP - 3381

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 8

ER -