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Evidence for the ke...
Evidence for the key role of the adipocyte cGMP-inhibited cAMP phosphodiesterase in the antilipolytic action of insulin
- Article/chapterEnglish1995
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LIBRIS-ID:oai:lup.lub.lu.se:a54e8369-f3d5-4c56-a072-bc9953d8f482
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https://lup.lub.lu.se/record/1109561URI
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https://doi.org/10.1016/0167-4889(94)00237-9DOI
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Language:English
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Summary in:English
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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.
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Ridderstråle, MartinLund University,Lunds universitet,Diabetes - klinisk obesitasforskning,Forskargrupper vid Lunds universitet,Diabetes - Clinical Obesity,Lund University Research Groups(Swepub:lu)endo-mri
(author)
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Degerman, EvaLund University,Lunds universitet,Signaltransduktionsforskning,Forskargrupper vid Lunds universitet,Insulin Signal Transduction,Lund University Research Groups(Swepub:lu)medk-ede
(author)
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Ekholm, Dag
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Smith, Carolyn J
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Manganiello, Vincent C
(author)
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Belfrage, PerLund University,Lunds universitet,Signaltransduktionsforskning,Forskargrupper vid Lunds universitet,Insulin Signal Transduction,Lund University Research Groups(Swepub:lu)medk-pbe
(author)
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Törnqvist, Hans
(author)
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Diabetes - klinisk obesitasforskningForskargrupper vid Lunds universitet
(creator_code:org_t)
Related titles
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In:Biochimica et Biophysica Acta: Elsevier BV1266:1, s. 101-1070006-3002
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In:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research: Elsevier BV1266:1, s. 101-1070167-4889
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