Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice
Open accessAbstract
Aims/hypothesis 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/interpretation Our data suggest that muscle ELVs might have an endocrine effect and could participate in adaptations in beta cell mass during insulin resistance.
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SkM-released ELVs might transmit signals to the pancreas during the development of insulin-resistance.
“These data suggested for the first time that SkM-released ELVs might transmit signals to the pancreas during the development of insulin-resistance.”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Jalabert et al., 2016
ELVs collected from conditioned medium of SkM explants from DIO mice induce specific transcriptional signatures in pancreatic MIN6B1 recipient cells compared to SkM-ELVs from NCD mice.
“ELVs collected from conditioned medium of SkM explants from DIO mice induced specific transcriptional signatures in pancreatic MIN6B1 recipient cells compared to SkM-ELVs from NCD mice.”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Jalabert et al., 2016
SkM can release ELV in blood.
“these data strongly suggest that SkM can release ELV in blood”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Jalabert et al., 2016
Expressions of 460 mRNAs are significantly modulated, including genes involved in immune responses known to be affected in pancreatic islets of diabetic patients.
“Microarray data analyses showed that the expressions of 460 mRNAs were significantly modulated including genes involved in immune responses known to be affected in pancreatic islets of diabetic patients”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Jalabert et al., 2016
Muscle-released ELVs have a paracrine-like action.
“suggesting again a paracrine-like action of muscle-released ELVs.”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Jalabert et al., 2016
Twenty-four hours after injection of fluorescent ELVs in the right tibialis anterior, fluorescence is detected in the left TA and in the right quadriceps.
“Twenty-four hours after injection, fluorescence was detected in the left TA and in the right quadriceps too”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Jalabert et al., 2016
Intraperitoneal injections of fluorescent SkM-ELVs result in fluorescent labeling of 9 organs in mice.
“Intraperitoneal injections of fluorescent SkM-ELVs resulted in the fluorescent labeling of 9 organs in mice”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Jalabert et al., 2016
SkM-ELVs mediate the transfer of miRNAs from insulin-resistant muscles into MIN6B1 and affect the expression of proliferative genes such as Ptch1.
“Additional bioinformatic analyses combined with in vitro experiments demonstrated that SkM-ELVs mediated the transfer of miRNAs from insulin-resistant muscles into MIN6B1 and affected the expression of proliferative genes such as Ptch1”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Jalabert et al., 2016
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- Authors
- Jalabert, A., Vial, G., Guay, C., Wiklander, O. P. B., Nordin, J. Z., Aswad, H., Forterre, A., Meugnier, E., Pesenti, S., Regazzi, R., Danty-Berger, E., Ducreux, S., Vidal, H., El-Andaloussi, S., Rieusset, J., & Rome, S.
- Affiliations
- Inserm (FR)
- University of Lausanne (CH)
- Karolinska University Hospital (SE)
- Corresponding author
- Rome, Sophie
- ORCID
- Venue
- Diabetologia
- Published
- 2016-02-06
- Volume
- 59
- Issue
- 5
- Pages
- 1049-1058
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2260637370
- Cited by
- 177
- References
- 47
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 18 · 2023: 19 · 2022: 20 · 2021: 24 · 2020: 17 · 2019: 19 · 2018: 15 · 2017: 11 · 2016: 5
- FWCI
- 8.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- AstraZeneca
- Fondation pour la Recherche Médicale (DRM20101220456)
- Université de Lyon
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- exosome-like nanoparticles, skeletal muscle, pancreatic beta cells, insulin resistance, microRNA transfer, miR-16, PTCH1, islet development, beta-cell proliferation, diabetes mellitus
- MeSH terms
- Animals, Cell Line, Insulin Resistance, Male, Muscle, Skeletal, Muscle Fibers, Skeletal, MicroRNAs, Insulin-Secreting Cells, Mice, Exosomes
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