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

Eriksson, Hans; Ridderstråle, Martin LU ; Degerman, Eva LU ; Ekholm, Dag; Smith, Carolyn J; Manganiello, Vincent C; Belfrage, Per LU and Törnqvist, Hans (1995) In Biochimica et Biophysica Acta 1266(1). p.101-107
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adipocyte, cAMP-dependent protein kinase, Inhibitor, Insulin, Lipolysis, Phosphodiesterase
in
Biochimica et Biophysica Acta
volume
1266
issue
1
pages
101 - 107
publisher
Elsevier
external identifiers
  • pmid:7718614
  • scopus:0028918411
ISSN
0006-3002
DOI
10.1016/0167-4889(94)00237-9
language
English
LU publication?
yes
id
a54e8369-f3d5-4c56-a072-bc9953d8f482 (old id 1109561)
date added to LUP
2008-07-29 09:52:26
date last changed
2017-08-06 04:32:14
@article{a54e8369-f3d5-4c56-a072-bc9953d8f482,
  abstract     = {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.},
  author       = {Eriksson, Hans and Ridderstråle, Martin and Degerman, Eva and Ekholm, Dag and Smith, Carolyn J and Manganiello, Vincent C and Belfrage, Per and Törnqvist, Hans},
  issn         = {0006-3002},
  keyword      = {Adipocyte,cAMP-dependent protein kinase,Inhibitor,Insulin,Lipolysis,Phosphodiesterase},
  language     = {eng},
  number       = {1},
  pages        = {101--107},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta},
  title        = {Evidence for the key role of the adipocyte cGMP-inhibited cAMP phosphodiesterase in the antilipolytic action of insulin},
  url          = {http://dx.doi.org/10.1016/0167-4889(94)00237-9},
  volume       = {1266},
  year         = {1995},
}