Elastin-Derived Peptides Are New Regulators of Insulin Resistance Development in Mice

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 11; pp. 3807 - 3816
• Main Authors: BLAISE, Sébastien, ROMIER, Béatrice, TARPIN, Michel, MARTINY, Laurent, GARBAR, Christian, DAUCHEZ, Manuel, DEBELLE, Laurent, DURLACH, Vincent, KAWECKI, Charlotte, GHIRARDI, Maxime, RABENOELINA, Fanja, BAUD, Stéphanie, DUCA, Laurent, MAURICE, Pascal, HEINZ, Andrea, SCHMELZER, Christian E. H
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.11.2013
• Subjects: Animals; Biological and medical sciences; Cardiovascular disease; Correlation analysis; Development and progression; Diabetes. Impaired glucose tolerance; Elastin; Elastin - metabolism; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy Metabolism - drug effects; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic aspects; Genetic regulation; Glucose; Hyperglycemia - chemically induced; Insulin resistance; Insulin Resistance - physiology; Life Sciences; Male; Medical sciences; Mice; Mice, Inbred C57BL; Musculoskeletal system; N-Acetylneuraminic Acid - analogs & derivatives; N-Acetylneuraminic Acid - pharmacology; Neuraminidase - metabolism; Oligopeptides - pharmacology; Original Research; Peptide Fragments - pharmacology; Peptides; Physiological aspects; Receptor, Insulin - metabolism; Receptors, Cell Surface - metabolism; France; Endocrinopathy; Peptides; Diabetes mellitus; Elastin; Rodentia; Metabolic diseases; Target tissue resistance; Vertebrata; Mammalia; Mouse; Animal; Development; Insulin resistance
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db13-0508

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.