GLUTADIAB

Targeting Glutamine Metabolism to prevent Diabetic Cardiovascular Complications

Glutamine metabolism and macrophage polarization.

In M1 macrophages, succinate accumulates due to glutamine-dependent anerplerosis and the GABA shunt. In M2 macrophages, α-ketoglutarate generated from glutaminolysis is essential for OXPHOS and FAO. Glutamine also supports M2 macrophage polarization through the glutamine–UDP-GlcNAc pathway. Also, M2 macrophages have a potential isocitrate to α-ketoglutarate conversion breakpoint in the metabolic flow of the TCA cycle.

Diabetes and related CV disease are associated to exacerbated inflammation, and an activation into a pro-inflammatory status of myeloid cells. Glutamine (Glut) is a critical fuel for the TCA cycle, a key regulatory checkpoint in macrophage polarization. The reported decreased [Glut] in T2D could reflect aberrant glutaminolysis of blood monocytes. The generated metabolites may trigger molecular mechanisms of pro-inflammatory polarization of monocytes in diabetes associated CV complications.

The aim of this project is to elucidate the molecular determinants involved in orchestrating the reprogramming of monocytes polarization in diabetes associated cardiovascular complications.

Team members

A new article from Cécile Haumaitre and collaborators discusses the origin of pancreatic lesions associated with pancreatic cancer

Diabetes Institute, From inflammation to cancer in digestive diseases, Publications

Pancreatic ductal adenocarcinoma is currently the fourth leading cause of cancer death worldwide. It is projected to become the second leading cause of cancer death by 2030. Unfortunately, PDAC is often diagnosed at an advanced stage, resulting in a 5-year survival rate of less than 10%. Since the most common precancerous lesions of PDAC are currently not clinically detectable, understanding the mechanisms that lead to their formation and progression is crucial to enabling early diagnosis and more effective therapeutic intervention.