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Glucose in the hypothalamic paraventricular nucleus regulates GLP-1 release
File(s)
Author(s)
Ma, Yue
Ratnasabapathy, Risheka
De Backer, Ivan
Izzi-Engbeaya, Chioma
Nguyen-Tu, Marie-sophie
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.
Date Issued
2020-04-23
Date Acceptance
2020-03-25
Citation
JCI insight, 2020, 5 (8)
URI
DOI
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
Medical Research Council (MRC)
Grant Number
MR/N020472/1
Subjects
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
Date Publish Online
2020-03-31