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Photo: KG Pressfoto

Marju Orho-Melander

Professor

Photo: KG Pressfoto

Transcriptional regulation of the miR-212/miR-132 cluster in insulin-secreting β-cells by cAMP-regulated transcriptional co-activator 1 and salt-inducible kinases.

Author

  • Helena Malm
  • Ines Mollet
  • Christine Berggreen
  • Marju Orho-Melander
  • Jonathan Esguerra
  • Olga Göransson
  • Lena Eliasson

Summary, in English

MicroRNAs are central players in the control of insulin secretion, but their transcriptional regulation is poorly understood. Our aim was to investigate cAMP-mediated transcriptional regulation of the miR-212/miR-132 cluster and involvement of further upstream proteins in insulin secreting β-cells. cAMP induced by forskolin+IBMX or GLP-1 caused increased expression of miR-212/miR-132, and elevated phosphorylation of cAMP-response-element-binding-protein (CREB)/Activating-transcription-factor-1 (ATF1) and Salt-Inducible-Kinases (SIKs). CyclicAMP-Regulated Transcriptional Co-activator-1 (CRTC1) was concomitantly dephosphorylated and translocated to the nucleus. Silencing of miR-212/miR-132 reduced, and overexpression of miR-212 increased, glucose-stimulated insulin secretion. Silencing of CRTC1 expression resulted in decreased insulin secretion and miR-212/miR-132 expression, while silencing or inhibition of SIKs was associated with increased expression of the microRNAs and dephosphorylation of CRTC1. CRTC1 protein levels were reduced after silencing of miR-132, suggesting feed-back regulation. Our data propose cAMP-dependent co-regulation of miR-212/miR-132, in part mediated through SIK-regulated CRTC1, as an important factor for fine-tuned regulation of insulin secretion.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • Protein Phosphorylation
  • Diabetes - Cardiovascular Disease
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2016-01-13

Language

English

Pages

23-33

Publication/Series

Molecular and Cellular Endocrinology

Volume

424

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis
  • Protein Phosphorylation
  • Diabetes - Cardiovascular Disease

ISBN/ISSN/Other

  • ISSN: 1872-8057