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Eva Degerman

Eva Degerman

Professor

Eva Degerman

Insulin induces Thr484 phosphorylation and stabilization of SIK2 in adipocytes

Author

  • Johanna Säll
  • Florentina Negoita
  • Björn Hansson
  • Franziska Kopietz
  • Wilhelm Linder
  • Annie M L Pettersson
  • Mikael Ekelund
  • Jurga Laurencikiene
  • Eva Degerman
  • Karin G Stenkula
  • Olga Göransson

Summary, in English

AIMS/HYPOTHESIS: Salt-inducible kinase 2 (SIK2) is downregulated in adipose tissue from obese or insulin-resistant individuals and inhibition of SIK isoforms results in reduced glucose uptake and insulin signalling in adipocytes. However, the regulation of SIK2 itself in response to insulin in adipocytes has not been studied in detail. The aim of our work was to investigate effects of insulin on various aspects of SIK2 function in adipocytes.

METHODS: Primary adipocytes were isolated from human subcutaneous and rat epididymal adipose tissue. Insulin-induced phosphorylation of SIK2 and HDAC4 was analyzed using phosphospecific antibodies and changes in the catalytic activity of SIK2 with in vitro kinase assay. SIK2 protein levels were analyzed in primary adipocytes treated with the proteasome inhibitor MG132.

RESULTS: We have identified a novel regulatory pathway of SIK2 in adipocytes, which involves insulin-induced phosphorylation at Thr484. This phosphorylation is impaired in individuals with a reduced insulin action. Insulin stimulation does not affect SIK2 catalytic activity or cellular activity towards HDAC4, but is associated with increased SIK2 protein levels in adipocytes.

CONCLUSION/INTERPRETATION: Our data suggest that downregulation of SIK2 in the adipose tissue of insulin-resistant individuals can partially be caused by impaired insulin signalling, which might result in defects in SIK2 expression and function.

Department/s

  • Diabetes - Epigenetics
  • Protein Phosphorylation
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Molecular Endocrinology
  • Glucose Transport and Protein Trafficking
  • Insulin Signal Transduction

Publishing year

2019

Language

English

Pages

73-80

Publication/Series

Cellular Signalling

Volume

55

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Status

Published

Project

  • Salt-inducible kinases in adipose tissue

Research group

  • Diabetes - Epigenetics
  • Protein Phosphorylation
  • Molecular Endocrinology
  • Glucose Transport and Protein Trafficking
  • Insulin Signal Transduction

ISBN/ISSN/Other

  • ISSN: 1873-3913