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Eva Degerman

Eva Degerman

Professor

Eva Degerman

Protein kinase B activity is required for the effects of insulin on lipid metabolism in adipocytes.

Author

  • Christine Berggreen
  • Amelie Gormand
  • Bilal Omar
  • Eva Degerman
  • Olga Göransson

Summary, in English

Protein kinase B is known to mediate a number of biological responses to insulin and growth factors, its role in glucose uptake being one of the most extensively studied. In this paper, we have employed a recently described allosteric inhibitor of PKB, Akti, to clarify the role of PKB in lipid metabolism in adipocytes - a subject that has received less attention. Pretreatment of primary rat and 3T3L1 adipocytes with Akti resulted in dose-dependent inhibition of PKB phosphorylation and activation in response to insulin, without affecting upstream insulin signaling (IR, IRS) or the insulin-induced PI3-K dependent activation of the ERK/RSK pathway. PKB activity was required for the insulin-induced activation of PDE3B and for the anti-lipolytic action of insulin. Moreover, inhibition of PKB activity resulted in a reduction in de novo lipid synthesis and in the ability of insulin to stimulate this process. The regulation of the rate-limiting lipogenic enzyme ACC by insulin through dephosphorylation of S79, which is a target for AMPK, was dependent on the presence of active PKB. Lastly, AMPK was shown to be phosphorylated by PKB on S485 in response to insulin and this was associated with a reduction in AMPK activity. In summary, we propose that PKB is required for the positive effects of insulin on lipid storage, and that regulation of PDE3B and AMPK by PKB is important for these effects. Key words: Akt, PDE3B, ACC, AMPK, lipogenesis.

Department/s

  • Protein Phosphorylation
  • Molecular Endocrinology
  • Insulin Signal Transduction

Publishing year

2009

Language

English

Pages

635-646

Publication/Series

American Journal of Physiology: Endocrinology and Metabolism

Volume

296

Document type

Journal article

Publisher

American Physiological Society

Topic

  • Physiology

Status

Published

Research group

  • Protein Phosphorylation
  • Molecular Endocrinology
  • Insulin Signal Transduction

ISBN/ISSN/Other

  • ISSN: 1522-1555