MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic β-Cell Proliferation

Sohei Tsukita, Tetsuya Yamada, Kei Takahashi, Yuichiro Munakata, Shinichiro Hosaka, Hironobu Takahashi, Junhong Gao, Yuta Shirai, Shinjiro Kodama, Yoichiro Asai, Takashi Sugisawa, Yumiko Chiba, Keizo Kaneko, Kenji Uno, Shojiro Sawada, Junta Imai, Hideki Katagiri

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)163-172
Number of pages10
JournalEBioMedicine
Volume15
DOIs
Publication statusPublished - 2017 Feb 1

Keywords

  • Cip/Kip family
  • Diabetes
  • Exosomes
  • MicroRNAs
  • β-cell regeneration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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