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

Cell reports 2020 Sep 15

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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. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

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. Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion. Cell reports. 2020 Sep 15;32(11):108141