Role of sphingolipid metabolism in the development of type 2 diabetes

One of the important functions of insulin-sensitive tissues is the storage of energy, allowing a transient nutritional independence from the external environment. Through hormonal or metabolic signals, many pathophysiological situations modify individual cell metabolism and the energy homeostasis of the whole organism. Insulin plays a key role in these regulations and the main theme of the research we conducted over the years concerns the action of this hormone in its target tissues under physiological and pathophysiological conditions. In particular, we contributed to understanding the cellular mechanisms involving fatty acid derivatives, such as ceramides in the appearance of insulin resistance in insulin-sensitive tissues, a key phenomenon in the development of type 2 diabetes. Among our most original results, we highlighted (i) the role of the protein kinase Akt in transducing the insulin signal to glucose transporters in muscle cells, (ii) the harmful mechanisms of action of ceramides on the insulin signaling pathway in muscle and fat cells (iii) a new potential target for the treatment of insulin resistance, the CERT ceramide transporter.

Using both lipidomic and cellular techniques, as well as transgenic mouse models, the objective of our current research projects is to counteract the deleterious effects of ceramides by highlighting new targets in the sphingolipid biosynthesis pathway.

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