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Eva Degerman

Eva Degerman

Professor

Eva Degerman

Evidence for the key role of the adipocyte cGMP-inhibited cAMP phosphodiesterase in the antilipolytic action of insulin

Author

  • Hans Eriksson
  • Martin Ridderstråle
  • Eva Degerman
  • Dag Ekholm
  • Carolyn J Smith
  • Vincent C Manganiello
  • Per Belfrage
  • Hans Törnqvist

Summary, in English

Enhancement of cAMP degradation by increased cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) activity is thought to be an important component of the mechanism whereby insulin counteracts catecholamine-induced lipolysis in adipocytes. In this study the selective cGI-PDE inhibitor OPC3911 was used to evaluate this role of cGI-PDE activation in intact rat adipocytes with special reference to changes in cAMP levels measured as cAMP-dependent protein kinase (cAMP-PK) activity ratios. OPC3911 completely blocked (IC50 = 0.3 microM) the maximal inhibitory effect of insulin on noradrenaline-induced lipolysis and the net dephosphorylation of hormone-sensitive lipase and other intracellular target proteins for insulin action, whereas insulin-induced lipogenesis was not changed. The effect of OPC3911 on cAMP-PK activity ratios at different levels of lipolysis achieved by noradrenaline stimulation revealed that the reduction of cAMP-PK caused by 1 nM insulin was completely blocked by 3 microM OPC3911. The effect of OPC3911 was not due to an excessive increase in cellular cAMP resulting in 'supramaximal' lipolysis unresponsive to insulin. These data demonstrate that reduction in cAMP levels by the activation of cGI-PDE may be sufficient to account for the antilipolytic action of insulin.

Department/s

  • Diabetes - Clinical Obesity
  • Insulin Signal Transduction

Publishing year

1995

Language

English

Pages

101-107

Publication/Series

Biochimica et biophysica acta

Volume

1266

Issue

1

Document type

Journal article

Publisher

Elsevier

Topic

  • Biological Sciences

Keywords

  • Adipocyte
  • cAMP-dependent protein kinase
  • Inhibitor
  • Insulin
  • Lipolysis
  • Phosphodiesterase

Status

Published

Research group

  • Diabetes - Clinical Obesity
  • Insulin Signal Transduction

ISBN/ISSN/Other

  • ISSN: 0006-3002