KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response | Zendy

Nabil Rabhi | Zendy; PierreDamien Denechaud | Zendy; Xavier Gromada | Zendy; Sarah Anissa Hannou | Zendy; Hongbo Zhang | Zendy; Talha Rashid | Zendy; Elisabet Salas | Zendy; Emmanuelle Durand | Zendy; Olivier Sand | Zendy; Amélie Bonnefond | Zendy; Loïc Yengo | Zendy; Carine Chavey | Zendy; Caroline Bonner | Zendy; Julie KerrConte | Zendy; Amar Abderrahmani | Zendy; Johan Auwerx | Zendy; Lluís Fajas | Zendy; Philippe Froguel | Zendy; JeanSébastien Annicotte | Zendy

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KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response

Author(s) -

Nabil Rabhi,

PierreDamien Denechaud,

Xavier Gromada,

Sarah Anissa Hannou,

Hongbo Zhang,

Talha Rashid,

Elisabet Salas,

Emmanuelle Durand,

Olivier Sand,

Amélie Bonnefond,

Loïc Yengo,

Carine Chavey,

Caroline Bonner,

Julie KerrConte,

Amar Abderrahmani,

Johan Auwerx,

Lluís Fajas,

Philippe Froguel,

JeanSébastien Annicotte

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.03.079

Subject(s) - unfolded protein response , endoplasmic reticulum , biology , beta cell , microbiology and biotechnology , pancreatic islets , gene expression , gene , regulation of gene expression , secretion , cell , islet , endocrinology , insulin , genetics

The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPR(er) gene expression appears in rodent and human type 2 diabetic (T2D) islets, the underlying molecular mechanisms remain unknown. We show here that germline and β cell-specific disruption of the lysine acetyltransferase 2B (Kat2b) gene in mice leads to impaired insulin secretion and glucose intolerance. Genome-wide analysis of Kat2b-regulated genes and functional assays reveal a critical role for Kat2b in maintaining UPR(er) gene expression and subsequent β cell function. Importantly, Kat2b expression is decreased in mouse and human diabetic β cells and correlates with UPR(er) gene expression in normal human islets. In conclusion, Kat2b is a crucial transcriptional regulator for adaptive β cell function during metabolic stress by controlling UPR(er) and represents a promising target for T2D prevention and treatment.

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