Diabetologie und Stoffwechsel 2018; 13(S 01): S5-S6
DOI: 10.1055/s-0038-1641772
Freie Vorträge
Freie Vorträge Endokrines Pankreas
Georg Thieme Verlag KG Stuttgart · New York

miR-132 controls mouse pancreatic beta cell proliferation and survival through the Pten/Akt/Foxo3 signaling

H Mziaut
1   DZD-Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at TU Dresden, Molecular Diabetology, Dresden, Germany
,
G Henniger
2   Faculty of Medicine, TU Dresden, Department of General, Thoracic and Vascular Surgery, Dresden, Germany
,
K Ganss
1   DZD-Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at TU Dresden, Molecular Diabetology, Dresden, Germany
,
S Hempel
2   Faculty of Medicine, TU Dresden, Department of General, Thoracic and Vascular Surgery, Dresden, Germany
,
S Wolk
2   Faculty of Medicine, TU Dresden, Department of General, Thoracic and Vascular Surgery, Dresden, Germany
,
J McChord
2   Faculty of Medicine, TU Dresden, Department of General, Thoracic and Vascular Surgery, Dresden, Germany
,
K Chowdhury
3   Max Planck Institute of Biophysical Chemistry, Göttingen, Göttingen, Germany
,
KP Knoch
1   DZD-Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at TU Dresden, Molecular Diabetology, Dresden, Germany
,
J Weitz
2   Faculty of Medicine, TU Dresden, Department of General, Thoracic and Vascular Surgery, Dresden, Germany
,
R Grützmann
4   University of Erlangen, Department of Surgery, Erlangen, Germany
,
C Pilarsky
4   University of Erlangen, Department of Surgery, Erlangen, Germany
,
M Solimena
1   DZD-Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at TU Dresden, Molecular Diabetology, Dresden, Germany
,
S Kersting
4   University of Erlangen, Department of Surgery, Erlangen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
26 April 2018 (online)

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    Aim:

    This study wás aimed to identify miRNAs and their downstream targets involved in regeneration of islet beta cells following partial pancreatectomy (PPx) in mice.

    Methods:

    RNA from laser capture microdissected (LCM) islets of PPx and sham-operated mice were profiled to identify miRNAs implicated in control of beta cell regeneration revealed miR-132 as one of the highly differentially expressed miRNAs. miR-132 targets were validated for their changed RNA, protein expression levels and signaling upon miR-132 knockdown or overexpression in MIN6 cells. The ability of miR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized miR-132 -/- and control mice.

    Results:

    PPx significantly increased the number of BrdU+/insulin+ positive islet cells. Microarray profiling revealed 14 miRNAs, including miR-132 and -141, to be significantly upregulated in LCM islets of PPx. Based on previous knowledge, we focused on miR-132. Downregulation of miR-132 in MIN6 cells reduced proliferation while enhancing the expression of pro-apoptotic genes, which were instead reduced upon miR-132 overexpression. Microarray profiling, RT-PCR and immunoblotting of miR-132 overexpressing MIN6 cells revealed the downregulated expression of Pten, with concomitant increased levels of pro-proliferative factors pAkt and pCreb as well as inactivation of pro-apoptotic Foxo3 via its phosphorylation. Finally, regeneration of beta cells following PPx was reduced in miR-132 -/- mice compared to control mice.

    Conclusions:

    Upregulation of miR-132 appears to be critical for regeneration of mouse islet beta cells in vivo through downregulation of its target Pten. Hence, the miR-132/Pten/Akt/Foxo3 pathway may represent a suitable target to enhance beta cell mass.


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