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Neuronatin regulates pancreatic β cell insulin content and secretion
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(2018) Neuronatin regulates pancreatic β cell insulin content and secretion. Journal of Clinical Investigation . doi:10.1172/JCI120115
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Official URL: http://dx.doi.org/10.1172/JCI120115
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.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Pancreatic beta cells, Obesity -- Physiological aspects | ||||||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Journal of Clinical Investigation | ||||||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | American Society for Clinical Investigation | ||||||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 1558-8238 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Official Date: | 4 June 2018 | ||||||||||||||||||||||||||||||||||||||||||||||||
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| Date of first compliant deposit: | 7 June 2018 | ||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1172/JCI120115 | ||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access | ||||||||||||||||||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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