Elastin-derived peptides are new regulators of insulin resistance development in mice

Sébastien Blaise; Béatrice Romier; Charlotte Kawecki; Maxime Ghirardi; Fanja Rabenoelina; Stéphanie Baud; Laurent Duca; Pascal Maurice; Andrea Heinz; Christian E H Schmelzer; Michel Tarpin; Laurent Martiny; Christian Garbar; Manuel Dauchez; Laurent Debelle; Vincent Durlach

doi:10.2337/db13-0508

Elastin-derived peptides are new regulators of insulin resistance development in mice

Sébastien Blaise, Béatrice Romier, Charlotte Kawecki, Maxime Ghirardi, Fanja Rabenoelina, Stéphanie Baud, Laurent Duca, Pascal Maurice, Andrea Heinz, Christian E H Schmelzer, Michel Tarpin, Laurent Martiny, Christian Garbar, Manuel Dauchez, Laurent Debelle, Vincent Durlach

56 Citations (Scopus)

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 b-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.

Original language	English
Journal	Diabetes
Volume	62
Issue number	11
Pages (from-to)	3807-16
Number of pages	10
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db13-0508
Publication status	Published - Nov 2013

Keywords

Animals
Elastin
Energy Metabolism
Hyperglycemia
Insulin Resistance
Male
Mice
Mice, Inbred C57BL
N-Acetylneuraminic Acid
Neuraminidase
Oligopeptides
Peptide Fragments
Receptor, Insulin
Receptors, Cell Surface
Journal Article
Research Support, Non-U.S. Gov't

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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 b-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.",

keywords = "Animals, Elastin, Energy Metabolism, Hyperglycemia, Insulin Resistance, Male, Mice, Mice, Inbred C57BL, N-Acetylneuraminic Acid, Neuraminidase, Oligopeptides, Peptide Fragments, Receptor, Insulin, Receptors, Cell Surface, Journal Article, Research Support, Non-U.S. Gov't",

author = "S{\'e}bastien Blaise and B{\'e}atrice Romier and Charlotte Kawecki and Maxime Ghirardi and Fanja Rabenoelina and St{\'e}phanie Baud and Laurent Duca and Pascal Maurice and Andrea Heinz and Schmelzer, {Christian E H} and Michel Tarpin and Laurent Martiny and Christian Garbar and Manuel Dauchez and Laurent Debelle and Vincent Durlach",

year = "2013",

month = nov,

doi = "10.2337/db13-0508",

language = "English",

volume = "62",

pages = "3807--16",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "11",

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TY - JOUR

T1 - Elastin-derived peptides are new regulators of insulin resistance development in mice

AU - Blaise, Sébastien

AU - Romier, Béatrice

AU - Kawecki, Charlotte

AU - Ghirardi, Maxime

AU - Rabenoelina, Fanja

AU - Baud, Stéphanie

AU - Duca, Laurent

AU - Maurice, Pascal

AU - Heinz, Andrea

AU - Schmelzer, Christian E H

AU - Tarpin, Michel

AU - Martiny, Laurent

AU - Garbar, Christian

AU - Dauchez, Manuel

AU - Debelle, Laurent

AU - Durlach, Vincent

PY - 2013/11

Y1 - 2013/11

N2 - 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 b-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.

AB - 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 b-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.

KW - Animals

KW - Elastin

KW - Energy Metabolism

KW - Hyperglycemia

KW - Insulin Resistance

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - N-Acetylneuraminic Acid

KW - Neuraminidase

KW - Oligopeptides

KW - Peptide Fragments

KW - Receptor, Insulin

KW - Receptors, Cell Surface

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.2337/db13-0508

DO - 10.2337/db13-0508

M3 - Journal article

C2 - 23919962

SN - 0012-1797

VL - 62

SP - 3807

EP - 3816

JO - Diabetes

JF - Diabetes

IS - 11

ER -

Elastin-derived peptides are new regulators of insulin resistance development in mice

Abstract

Keywords

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