Regenerating islet-derived protein 3α: A promising therapy for diabetes. Preliminary data in rodents and in humans
Aurélie Le Lay,
Erwann Philippe,
Fanny Roth,
Ana Rodriguez Sanchez-Archidona,
Florence Mehl,
Jessica Denom,
Rashmi Prasad,
Olof Asplund,
Ola Hansson,
Mark Ibberson,
Fabrizio Andreelli,
Lyse Santoro,
Paul Amouyal,
Gilles Amouyal,
Christian Brechot,
Laure Jamot,
Céline Cruciani-Guglielmacci,
Christophe Magnan
Affiliations
Aurélie Le Lay
The Healthy Aging Company, Incubateur Paris Biotech Santé, F-75014 Paris, France
Erwann Philippe
The Healthy Aging Company, Incubateur Paris Biotech Santé, F-75014 Paris, France
Fanny Roth
The Healthy Aging Company, Incubateur Paris Biotech Santé, F-75014 Paris, France
Ana Rodriguez Sanchez-Archidona
Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland
Florence Mehl
Vital-IT Group, SIB Swiss Institute for Bioinformatics, 1015 Lausanne, Switzerland
Jessica Denom
Université de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, France
Rashmi Prasad
Department of Clinical Sciences, Lund University, Malmö, Sweden
Olof Asplund
Department of Clinical Sciences, Lund University, Malmö, Sweden; Institute for Molecular Medicine Finland (FIMM), Helsinki University, Helsinki, Finland
Ola Hansson
Department of Clinical Sciences, Lund University, Malmö, Sweden
Mark Ibberson
Vital-IT Group, SIB Swiss Institute for Bioinformatics, 1015 Lausanne, Switzerland
Fabrizio Andreelli
Nutrition and Obesities; Systemic Approaches (NutriOmics), Sorbonne Université, INSERM; Pitié-Salpêtrière Hospital, Assistance Publique - Hopitaux de Paris, Paris, France
Lyse Santoro
The Healthy Aging Company, Incubateur Paris Biotech Santé, F-75014 Paris, France
Paul Amouyal
The Healthy Aging Company, Incubateur Paris Biotech Santé, F-75014 Paris, France
Gilles Amouyal
The Healthy Aging Company, Incubateur Paris Biotech Santé, F-75014 Paris, France
Christian Brechot
The Healthy Aging Company, Incubateur Paris Biotech Santé, F-75014 Paris, France; University of South Florida, Tampa, FL 33612, USA
Laure Jamot
The Healthy Aging Company, Incubateur Paris Biotech Santé, F-75014 Paris, France
Céline Cruciani-Guglielmacci
Université de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, France
Christophe Magnan
Université de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, France; Corresponding author.
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.
