title: Elastin-derived peptides are new regulators of insulin resistance development in mice.
abstract: Although it has long been established that the extracellular matrix acts as a mechanical support, its degradation products, which mainly accumulate during aging, have also been demonstrated to play an important role in cell physiology and the development of cardiovascular and metabolic diseases. In the current study, we show that elastin-derived peptides (EDPs) may be involved in the development of insulin resistance (IRES) in mice. In chow-fed mice, acute or chronic intravenous injections of EDPs induced hyperglycemic effects associated with glucose uptake reduction and IRES in skeletal muscle, liver, and adipose tissue. Based on in vivo, in vitro, and in silico approaches, we propose that this IRES is due to interaction between the insulin receptor (IR) and the neuraminidase-1 subunit of the elastin receptor complex triggered by EDPs. This interplay was correlated with decreased sialic acid levels on the β-chain of the IR and reduction of IR signaling. In conclusion, this is the first study to demonstrate that EDPs, which mainly accumulate with aging, may be involved in the insidious development of IRES.
authors.affiliation: Formations de Recherche en Evolution CNRS 3481, Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne Ardenne, UFR Sciences Exactes et Naturelles, Reims, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Blaise
authors.forename: Béatrice
authors.initials: B
authors.lastname: Romier
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kawecki
authors.forename: Maxime
authors.initials: M
authors.lastname: Ghirardi
authors.forename: Fanja
authors.initials: F
authors.lastname: Rabenoelina
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baud
authors.forename: Laurent
authors.initials: L
authors.lastname: Duca
authors.forename: Pascal
authors.initials: P
authors.lastname: Maurice
authors.forename: Andrea
authors.initials: A
authors.lastname: Heinz
authors.forename: Christian E H
authors.initials: CE
authors.lastname: Schmelzer
authors.forename: Michel
authors.initials: M
authors.lastname: Tarpin
authors.forename: Laurent
authors.initials: L
authors.lastname: Martiny
authors.forename: Christian
authors.initials: C
authors.lastname: Garbar
authors.forename: Manuel
authors.initials: M
authors.lastname: Dauchez
authors.forename: Laurent
authors.initials: L
authors.lastname: Debelle
authors.forename: Vincent
authors.initials: V
authors.lastname: Durlach
mesh_terms: D000818:Animals; D004549:Elastin / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D006943:Hyperglycemia / Q000139:chemically induced; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009439:Neuraminidase / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D004549:Elastin; D011972:Receptor, Insulin; C110128:Neu1 protein, mouse; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid
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