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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
Publishing year: 1995
Language: English
Pages: 101-107
Publication/Series: Biochimica et Biophysica Acta
Volume: 1266
Issue: 1
Document type: Journal article
Publisher: Elsevier

Abstract 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.

Keywords

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

Other

Published
  • Clinical Obesity
  • Insulin Signal Transduction
  • ISSN: 0006-3002
Eva Degerman
E-mail: eva [dot] degerman [at] med [dot] lu [dot] se

Professor

Insulin Signal Transduction

+46 46 222 85 83

+46 70 885 83 62

BMC C1121b

66

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00