Eric Hajduch PhD cell physiology
Course and current status
I was born in Paris, France. I received my Ph.D. degree, specialized in the regulation of the expression of glucose transporters in adipocytes, from the University of Paris VII, in 1995. Then, I spent 7 years in Dundee, Scotland, as a Postdoctoral Fellow to work on insulin signaling in muscle cells. Since 2004, I work as a Senior Researcher at the Institut National de la Santé et de la Recherche Médicale (INSERM), at the Centre de Recherche des Cordeliers, Paris. My current research is devoted to the study of the molecular mechanisms involved in insulin resistance induced by fatty acid derivatives, such as ceramide, in insulin sensitive tissues.
Scientific summary
Type 2 diabetes has become the biggest public health challenge of the 21st century with recent reports suggesting that we are eating ourselves into a diabetes epidemic. Type 2 diabetes is characterized by two major metabolic abnormalities: peripheral insulin résistance (liver, muscles and fat) and a deficit in insulin secretion (beta cells). Although we do not understand precisely interactions between these abnormalities, the final evolution towards hyperglycemia results from the incapacity of beta-cells to produce enough insulin to compensate peripheral insulin resistance.
Insulin resistance, which characterizes type 2 diabetes and obesity, is the consequence of the inhibition of insulin to act on its target tissues. It is clearly established that an increase in lipid content within peripheral tissues is responsible for the insulin resistance state by inducing the accumulation of intracellular signaling molecules that interfere with the insulin signalling pathway. Although lipotoxicity is often correlated with an increase in intracellular lipids, it is now well documented that lipid-derived metabolites are actually involved. In skeletal muscle, ceramide that is produced from palmitate is a key factor responsible for the onset of insulin resistance induced by lipid overload. Studies showed a positive correlation between the increase in muscle ceramide and a loss in insulin sensitivity. The importance of the deleterious action of ceramide was established in several recent studies that showed that pharmacological or genetic inhibition of the ceramide biosynthesis pathway restores insulin sensitivity in high-fat diet-fed animals. During the last 15 years, we were among the first to decipher the mechanisms by which ceramide acts negatively on the insulin signal in both muscle and fat cells.
At present, the main interest of my group is to understand how sphingolipids interfere with insulin signaling in skeletal muscle cells in vivo and in vitro in animal models and in humans.
Our ultimate goal is to find ways to counteract negative actions of ceramide which are responsible in part for insulin resistance and type 2 diabetes.
