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MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic β-Cell Proliferation.
- Source :
-
EBioMedicine [EBioMedicine] 2017 Feb; Vol. 15, pp. 163-172. Date of Electronic Publication: 2016 Dec 07. - Publication Year :
- 2017
-
Abstract
- Major symptoms of diabetes mellitus manifest, once pancreatic β-cell numbers have become inadequate. Although natural regeneration of β-cells after injury is very limited, bone marrow (BM) transplantation (BMT) promotes their regeneration through undetermined mechanism(s) involving inter-cellular (BM cell-to-β-cell) crosstalk. We found that two microRNAs (miRNAs) contribute to BMT-induced β-cell regeneration. Screening murine miRNAs in serum exosomes after BMT revealed 42 miRNAs to be increased. Two of these miRNAs (miR-106b-5p and miR-222-3p) were shown to be secreted by BM cells and increased in pancreatic islet cells after BMT. Treatment with the corresponding anti-miRNAs inhibited BMT-induced β-cell regeneration. Furthermore, intravenous administration of the corresponding miRNA mimics promoted post-injury β-cell proliferation through Cip/Kip family down-regulation, thereby ameliorating hyperglycemia in mice with insulin-deficient diabetes. Thus, these identified miRNAs may lead to the development of therapeutic strategies for diabetes.<br /> (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Bone Marrow Cells metabolism
Bone Marrow Transplantation
Calcium-Binding Proteins genetics
Carrier Proteins genetics
Cell Proliferation
Co-Repressor Proteins
Diabetes Mellitus, Experimental
Disease Models, Animal
Exosomes
Gene Expression Regulation
Islets of Langerhans metabolism
Mice
Nuclear Proteins
RNA Interference
Regeneration
Diabetes Mellitus, Type 1 blood
Diabetes Mellitus, Type 1 genetics
Hyperglycemia genetics
Insulin-Secreting Cells metabolism
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2352-3964
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- 27974246
- Full Text :
- https://doi.org/10.1016/j.ebiom.2016.12.002