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Eva Degerman

Eva Degerman

Professor

Eva Degerman

Inhibition of AMPK activity in response to insulin in adipocytes : involvement of AMPK pS485, PDEs, and cellular energy levels

Author

  • Franziska Kopietz
  • Kaja Rupar
  • Christine Berggreen
  • Johanna Säll
  • Didier Vertommen
  • Eva Degerman
  • Mark H. Rider
  • Olga Göransson

Summary, in English

Insulin resistance in obesity and type 2 diabetes has been shown to be associated with decreased de novo fatty acid (FA) synthesis in adipose tissue. It is known that insulin can acutely stimulate FA synthesis in adipocytes; however, the mechanisms underlying this effect are unclear. The rate-limiting step in FA synthesis is catalyzed by acetyl-CoA carboxylase (ACC), known to be regulated through inhibitory phosphorylation at S79 by the AMP-activated protein kinase (AMPK). Previous results from our laboratory showed an inhibition of AMPK activity by insulin, which was accompanied by PKB-dependent phosphorylation of AMPK at S485. However, whether the S485 phosphorylation is required for insulin-induced inhibition of AMPK or other mechanisms underlie the reduced kinase activity is not known. To investigate this, primary rat adipocytes were transduced with a recombinant adenovirus encoding AMPK-WT or a nonphosphorylatable AMPK S485A mutant. AMPK activity measurements by Western blot analysis and in vitro kinase assay revealed that WT and S485A AMPK were inhibited to a similar degree by insulin, indicating that AMPK S485 phosphorylation is not required for insulin-induced AMPK inhibition. Further analysis suggested an involvement of decreased AMP-to-ATP ratios in the insulin-induced inhibition of AMPK activity, whereas a possible contribution of phosphodiesterases was excluded. Furthermore, we show that insulin-induced AMPK S485 phosphorylation also occurs in human adipocytes, suggesting it to be of an importance yet to be revealed. Altogether, this study increases our understanding of how insulin regulates AMPK activity, and with that, FA synthesis, in adipose tissue.

Department/s

  • Protein Phosphorylation
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Diabetes - Epigenetics
  • Department of Experimental Medical Science
  • Insulin Signal Transduction

Publishing year

2020

Language

English

Pages

459-471

Publication/Series

American Journal of Physiology - Endocrinology and Metabolism

Volume

319

Issue

3

Document type

Journal article

Publisher

American Physiological Society

Topic

  • Endocrinology and Diabetes

Keywords

  • adipocytes
  • AMP-activated protein kinase
  • fatty acid synthesis
  • insulin
  • pS485

Status

Published

Research group

  • Protein Phosphorylation
  • Diabetes - Epigenetics
  • Insulin Signal Transduction

ISBN/ISSN/Other

  • ISSN: 1522-1555