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  • Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion.

Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion.

Cell reports (2020-09-17)
Karima Drareni, Raphaëlle Ballaire, Fawaz Alzaid, Andreia Goncalves, Catherine Chollet, Serena Barilla, Jean-Louis Nguewa, Karine Dias, Sophie Lemoine, Jean-Pierre Riveline, Ronan Roussel, Elise Dalmas, Gilberto Velho, Eckardt Treuter, Jean-François Gautier, Nicolas Venteclef
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, ≥98% (TLC), powder
Sigma-Aldrich
Dexamethasone, ≥98% (HPLC), powder
Roche
In Situ Cell Death Detection Kit, TMR red, sufficient for ≤50 tests
Millipore
MILLIPLEX® Mouse Adipocyte Magnetic Panel - Endocrine Multiplex Assay, The analytes available for this multiplex kit are: Adiponectin, IL-6, Leptin, MCP-1, PAI-1 (Total), Resistin, TNF-α.