Insulin signaling, glucose sensing and glucotoxicity

We are performing metabolic and transcriptional studies of the regulatory role of the insulin receptor (IR), the key enzyme of O-GlcNAcylation (OGT) and the glucose-sensitive transcription factor ChREBP in cells important for glucose-sensing and/or energy homeostasis, such as hepatocytes, intestinal and immune cells. Our scientific goal is to unravel how these proteins, not only by controlling glucose flux and/or insulin sensitivity, but also the release of systemic proteins (hepatokines, cytokines, gastro-intestinal peptides), modulate the inter-organ dialogue to tightly control metabolic homeostasis. To do so, we take advantage of unique genetic mouse models developed by our group, in which our targets have been deleted in a cell-specific manner. Whenever possible, we aim at translating our studies to humans through various collaborations with clinicians (RHU-Quid NASH, Tissue bank BioDIGE).
Our major objectives are therefore to:
– study the relationships between gut insulin resistance, intestinal barrier function and inflammation
– investigate the role of OGT in hepatic and inflammatory diseases
– explore how ChREBP affects the inter-organ network to control energy homeostasis