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Glucose in the hypothalamic paraventricular nucleus regulates GLP-1 release

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Title: Glucose in the hypothalamic paraventricular nucleus regulates GLP-1 release
Authors: Ma, Y
Ratnasabapathy, R
De Backer, I
Izzi-Engbeaya, C
Nguyen-Tu, M-S
Cuenco, J
Jones, B
John, C
Lam, B
Rutter, G
Yeo, G
Dhillo, W
Gardiner, J
Item Type: Journal Article
Abstract: Glucokinase (GK) is highly expressed in the hypothalamic paraventricular nucleus (PVN); however, its role is currently unknown. We found that GK in the PVN acts as part of a glucose-sensing mechanism within the PVN that regulates glucose homeostasis by controlling glucagon-like peptide 1 (GLP-1) release. GLP-1 is released from enteroendocrine L cells in response to oral glucose. Here we identify a brain mechanism critical to the release of GLP-1 in response to oral glucose. We show that increasing expression of GK or injection of glucose into the PVN increases GLP-1 release in response to oral glucose. On the contrary, decreasing expression of GK or injection of nonmetabolizable glucose into the PVN prevents GLP-1 release. Our results demonstrate that gluco-sensitive GK neurons in the PVN are critical to the response to oral glucose and subsequent release of GLP-1.
Issue Date: 23-Apr-2020
Date of Acceptance: 25-Mar-2020
URI: http://hdl.handle.net/10044/1/79031
DOI: 10.1172/jci.insight.132760
ISSN: 2379-3708
Publisher: American Society for Clinical Investigation
Journal / Book Title: JCI insight
Volume: 5
Issue: 8
Copyright Statement: Copyright: © 2020, Ma et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/N020472/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
PEPTIDE-1 SECRETION
STIMULATES GLP-1
GIP SECRETION
GLUCOKINASE
BRAIN
RATS
NEUROTRANSMITTERS
CELLS
PURIFICATION
HOMEOSTASIS
Diabetes
Endocrinology
Glucose metabolism
Neuroscience
Peptides
Publication Status: Published
Article Number: ARTN e132760
Online Publication Date: 2020-03-31
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Faculty of Medicine