Millership, SJ;
Xavier, GDS;
Choudhury, AI;
Bertazzo, S;
Chabosseau, P;
Pedroni, SMA;
Irvine, EE;
... Withers, DJ; + view all
(2018)
Neuronatin regulates pancreatic beta cell insulin content and secretion.
The Journal of Clinical Investigation
, 128
(8)
pp. 3369-3381.
10.1172/JCI120115.
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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.
| Type: | Article |
|---|---|
| Title: | Neuronatin regulates pancreatic beta cell insulin content and secretion |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/JCI120115 |
| Publisher version: | https://doi.org/10.1172/JCI120115 |
| Language: | English |
| Additional information: | This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10054742 |
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