title: Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice.
abstract: OBJECTIVE
  The crosstalk between skeletal muscle (SkM) and beta cells plays a role in diabetes aetiology. In this study, we have investigated whether SkM-released exosome-like vesicles (ELVs) can be taken up by pancreatic beta cells and can deliver functional cargoes.
  
  
  METHODS
  Mice were fed for 16 weeks with standard chow diet (SCD) or with standard diet enriched with 20% palmitate (HPD) and ELVs were purified from quadriceps muscle. Fluorescent ELVs from HPD or SCD quadriceps were injected i.v. or intramuscularly (i.m.) into mice to determine their biodistributions. Micro (mi)RNA quantification in ELVs was determined using quantitative real-time RT-PCR (qRT-PCR)-based TaqMan low-density arrays. Microarray analyses were performed to determine whether standard diet ELVs (SD-ELVs) and high palmitate diet ELVs (HPD-ELVs) induced specific transcriptional signatures in MIN6B1 cells.
  
  
  RESULTS
  In vivo, muscle ELVs were taken up by pancreas, 24 h post-injection. In vitro, both SD-ELVs and HPD-ELVs transferred proteins and miRNAs to MIN6B1 cells and modulated gene expressions whereas only HPD-ELVs induced proliferation of MIN6B1 cells and isolated islets. Bioinformatic analyses suggested that transferred HPD-ELV miRNAs may participate in these effects. To validate this, we demonstrated that miR-16, which is overexpressed in HPD-ELVs, was transferred to MIN6B1 cells and regulated Ptch1, involved in pancreas development. In vivo, islets from HPD mice showed increased size and altered expression of genes involved in development, including Ptch1, suggesting that the effect of palm oil on islet size in vivo was reproduced in vitro by treating beta cells with HPD-ELVs.
  
  
  CONCLUSIONS
  Our data suggest that muscle ELVs might have an endocrine effect and could participate in adaptations in beta cell mass during insulin resistance.
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Audrey
authors: A
authors: Jalabert
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Guillaume
authors: G
authors: Vial
authors: Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
authors: Claudiane
authors: C
authors: Guay
authors: Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden.
authors: Oscar P B
authors: OP
authors: Wiklander
authors: Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden.
authors: Joel Z
authors: JZ
authors: Nordin
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Hala
authors: H
authors: Aswad
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Alexis
authors: A
authors: Forterre
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Emmanuelle
authors: E
authors: Meugnier
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Sandra
authors: S
authors: Pesenti
authors: Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
authors: Romano
authors: R
authors: Regazzi
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Emmanuelle
authors: E
authors: Danty-Berger
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Sylvie
authors: S
authors: Ducreux
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Hubert
authors: H
authors: Vidal
authors: Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden.|Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
authors: Samir
authors: S
authors: El-Andaloussi
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France.
authors: Jennifer
authors: J
authors: Rieusset
authors: CarMeN laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, 69600, Oullins, France. srome@univ-lyon1.fr.
authors: Sophie
authors: S
authors: Rome
mesh_terms: D000818:Animals; D002460:Cell Line; D055354:Exosomes / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*
chemical_list: D035683:MicroRNAs
keywords: Beta cells; Diabetes; Exosomes; Extracellular vesicles; High-fat diet; Insulin resistance; Palmitate; Skeletal muscle; microRNAs