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Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion
- Source :
- Cell Reports, Cell Reports, Elsevier Inc, 2020, 32, pp.108141-. ⟨10.1016/j.celrep.2020.108141⟩, Cell Reports, 2020, 32, pp.108141-. ⟨10.1016/j.celrep.2020.108141⟩
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- Summary 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.<br />Graphical Abstract<br />Highlights • GPS2 expression in adipose tissue is associated with insulin secretion rate in humans • Loss of GPS2 in adipocytes impacts on insulin secretion upon diet-induced obesity • Beta cell dysfunction in Gps2 KO mice is governed by islet inflammation • This beta cell maladaptation in Gps2 KO mice is mediated by adipose tissue secretome<br />Appropriate insulin secretion is governed through organ crosstalk. Drareni et al. show that GPS2 expression in 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 in obese mice.
- Subjects :
- Male
insulin
G protein pathway suppressor 2
GPS2
Adipose Tissue, White
[SDV]Life Sciences [q-bio]
Adipocytes, White
Mice
Insulin-Secreting Cells
Report
Glucose Intolerance
Insulin Secretion
Animals
Obesity
pancreas
organ crosstalk
Inflammation
Mice, Knockout
Intracellular Signaling Peptides and Proteins
adipose tissue
Mice, Inbred C57BL
[SDV] Life Sciences [q-bio]
beta cells
Glucose
Diabetes Mellitus, Type 2
Female
type 2 diabetes
Insulin Resistance
transcriptional coregulator
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Database :
- OpenAIRE
- Journal :
- Cell Reports, Cell Reports, Elsevier Inc, 2020, 32, pp.108141-. ⟨10.1016/j.celrep.2020.108141⟩, Cell Reports, 2020, 32, pp.108141-. ⟨10.1016/j.celrep.2020.108141⟩
- Accession number :
- edsair.pmid.dedup....d1e221da4133c8eca16947227ad44e17