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Date publication

février 2024

Journal

Journal of physiology and biochemistry

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BLAISE Sébastien , Pr DAUCHEZ Manuel , Dr DUCA Laurent , Pr MARTINY Laurent , Pr BAUD Stéphanie , Dr BENNASROUNE Amar


Tous les auteurs :
Guillot A, Toussaint K, Ebersold L, ElBtaouri H, Thiebault E, Issad T, Peiretti F, Maurice P, Sartelet H, Bennasroune A, Martiny L, Dauchez M, Duca L, Durlach V, Romier B, Baud S, Blaise S

Résumé

The insulin receptor (IR) plays an important role in insulin signal transduction, the defect of which is believed to be the root cause of type 2 diabetes. In 3T3-L1 adipocytes as in other cell types, the mature IR is a heterotetrameric cell surface glycoprotein composed of two α subunits and two β subunits. Our objective in our study, is to understand how the desialylation of N-glycan chains, induced by elastin-derived peptides, plays a major role in the function of the IR. Using the 3T3-L1 adipocyte line, we show that removal of the sialic acid from N-glycan chains (N893 and N908), induced by the elastin receptor complex (ERC) and elastin derived-peptides (EDPs), leads to a decrease in the autophosphorylation activity of the insulin receptor. We demonstrate by molecular dynamics approaches that the absence of sialic acids on one of these two sites is sufficient to generate local and general modifications of the structure of the IR. Biochemical approaches highlight a decrease in the interaction between insulin and its receptor when ERC sialidase activity is induced by EDPs. Therefore, desialylation by EDPs is synonymous with a decrease of IR sensitivity in adipocytes and could thus be a potential source of insulin resistance associated with diabetic conditions.

Mots clés

Elastin-derived-peptides, Insulin receptor, Insulin resistance, Ligand-receptor affinity, N-glycan

Référence

J Physiol Biochem. 2024 02 23;: