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Regenerating islet-derived protein 3α : A promising therapy for diabetes. Preliminary data in rodents and in humans

Le Lay, Aurélie ; Philippe, Erwann ; Roth, Fanny ; Sanchez-Archidona, Ana Rodriguez ; Mehl, Florence ; Denom, Jessica ; Prasad, Rashmi LU ; Asplund, Olof LU ; Hansson, Ola LU orcid and Ibberson, Mark , et al. (2022) In Heliyon 8(7).
Abstract

The aim of our study was to test the hypothesis that administration of Regenerating islet-derived protein 3α (Reg3α), a protein described as having protective effects against oxidative stress and anti-inflammatory activity, could participate in the control of glucose homeostasis and potentially be a new target of interest in the treatment of type 2 diabetes. To that end the recombinant human Reg3α protein was administered for one month in insulin-resistant mice fed high fat diet. We performed glucose and insulin tolerance tests, assayed circulating chemokines in plasma and measured glucose uptake in insulin sensitive tissues. We evidenced an increase in insulin sensitivity during an oral glucose tolerance test in ALF-5755 treated mice... (More)

The aim of our study was to test the hypothesis that administration of Regenerating islet-derived protein 3α (Reg3α), a protein described as having protective effects against oxidative stress and anti-inflammatory activity, could participate in the control of glucose homeostasis and potentially be a new target of interest in the treatment of type 2 diabetes. To that end the recombinant human Reg3α protein was administered for one month in insulin-resistant mice fed high fat diet. We performed glucose and insulin tolerance tests, assayed circulating chemokines in plasma and measured glucose uptake in insulin sensitive tissues. We evidenced an increase in insulin sensitivity during an oral glucose tolerance test in ALF-5755 treated mice vs controls and decreased the pro-inflammatory cytokine C-X-C Motif Chemokine Ligand 5 (CXCL5). We also demonstrated an increase in glucose uptake in skeletal muscle. Finally, correlation studies using human and mouse muscle biopsies showed negative correlation between intramuscular Reg3α mRNA expression (or its murine isoform Reg3γ) and insulin resistance. Thus, we have established the proof of concept that Reg3α could be a novel molecule of interest in the treatment of T2D by increasing insulin sensitivity via a skeletal muscle effect.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Heliyon
volume
8
issue
7
article number
e09944
publisher
Elsevier
external identifiers
  • scopus:85134473655
  • pmid:35874080
ISSN
2405-8440
DOI
10.1016/j.heliyon.2022.e09944
language
English
LU publication?
yes
additional info
© 2022 Published by Elsevier Ltd.
id
4afcda36-19c6-4b55-9e2e-7418805baed7
date added to LUP
2022-08-03 19:04:52
date last changed
2024-04-18 10:51:21
@article{4afcda36-19c6-4b55-9e2e-7418805baed7,
  abstract     = {{<p>The aim of our study was to test the hypothesis that administration of Regenerating islet-derived protein 3α (Reg3α), a protein described as having protective effects against oxidative stress and anti-inflammatory activity, could participate in the control of glucose homeostasis and potentially be a new target of interest in the treatment of type 2 diabetes. To that end the recombinant human Reg3α protein was administered for one month in insulin-resistant mice fed high fat diet. We performed glucose and insulin tolerance tests, assayed circulating chemokines in plasma and measured glucose uptake in insulin sensitive tissues. We evidenced an increase in insulin sensitivity during an oral glucose tolerance test in ALF-5755 treated mice vs controls and decreased the pro-inflammatory cytokine C-X-C Motif Chemokine Ligand 5 (CXCL5). We also demonstrated an increase in glucose uptake in skeletal muscle. Finally, correlation studies using human and mouse muscle biopsies showed negative correlation between intramuscular Reg3α mRNA expression (or its murine isoform Reg3γ) and insulin resistance. Thus, we have established the proof of concept that Reg3α could be a novel molecule of interest in the treatment of T2D by increasing insulin sensitivity via a skeletal muscle effect.</p>}},
  author       = {{Le Lay, Aurélie and Philippe, Erwann and Roth, Fanny and Sanchez-Archidona, Ana Rodriguez and Mehl, Florence and Denom, Jessica and Prasad, Rashmi and Asplund, Olof and Hansson, Ola and Ibberson, Mark and Andreelli, Fabrizio and Santoro, Lyse and Amouyal, Paul and Amouyal, Gilles and Brechot, Christian and Jamot, Laure and Cruciani-Guglielmacci, Céline and Magnan, Christophe}},
  issn         = {{2405-8440}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{Elsevier}},
  series       = {{Heliyon}},
  title        = {{Regenerating islet-derived protein 3α : A promising therapy for diabetes. Preliminary data in rodents and in humans}},
  url          = {{http://dx.doi.org/10.1016/j.heliyon.2022.e09944}},
  doi          = {{10.1016/j.heliyon.2022.e09944}},
  volume       = {{8}},
  year         = {{2022}},
}