Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion.
Adipocytes, White
/ metabolism
Adipose Tissue
/ metabolism
Adipose Tissue, White
/ metabolism
Animals
Diabetes Mellitus, Type 2
/ metabolism
Female
Glucose
/ metabolism
Glucose Intolerance
/ metabolism
Inflammation
/ metabolism
Insulin
/ metabolism
Insulin Resistance
/ genetics
Insulin Secretion
/ physiology
Insulin-Secreting Cells
/ metabolism
Intracellular Signaling Peptides and Proteins
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity
/ metabolism
G protein pathway suppressor 2
GPS2
adipose tissue
beta cells
insulin
organ crosstalk
pancreas
transcriptional coregulator
type 2 diabetes
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
15 09 2020
15 09 2020
Historique:
received:
14
01
2020
revised:
03
07
2020
accepted:
21
08
2020
entrez:
16
9
2020
pubmed:
17
9
2020
medline:
1
5
2021
Statut:
ppublish
Résumé
Glucose homeostasis is maintained through organ crosstalk that regulates secretion of insulin to keep blood glucose levels within a physiological range. In type 2 diabetes, this coordinated response is altered, leading to a deregulation of beta cell function and inadequate insulin secretion. Reprogramming of white adipose tissue has a central role in this deregulation, but the critical regulatory components remain unclear. Here, we demonstrate that expression of the transcriptional coregulator GPS2 in white adipose tissue is correlated with insulin secretion rate in humans. The causality of this relationship is confirmed using adipocyte-specific GPS2 knockout mice, in which inappropriate secretion of insulin promotes glucose intolerance. This phenotype is driven by adipose-tissue-secreted factors, which cause increased pancreatic islet inflammation and impaired beta cell function. Thus, our study suggests that, in mice and in humans, GPS2 controls the reprogramming of white adipocytes to influence pancreatic islet function and insulin secretion.
Identifiants
pubmed: 32937117
pii: S2211-1247(20)31130-X
doi: 10.1016/j.celrep.2020.108141
pmc: PMC7495095
pii:
doi:
Substances chimiques
GPS2 protein, mouse
0
Insulin
0
Intracellular Signaling Peptides and Proteins
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108141Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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