Hormonal regulation of phosphodiesterase 3B in adipocytes

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Insulin induced activation of the cAMP degrading enzyme phosphodiesterase (PDE) 3B in adipocytes is important for insulin mediated inhibition of lipolysis. The aim of this thesis was to contribute with knowledge on the acute activation of PDE3B in response to insulin and catecholamines in adipocytes. The activation of PDE3B was investigated from three different perspectives namely; phosphorylation of PDE3B, localization of PDE3B and PDE3B interactions with other proteins. As models to study activation of PDE3B we used primary rat and mouse adipocytes, 3T3-L1 adipocytes and caveolin-1 knock out mouse adipocytes.

The study on PDE3B phosphorylation shows that PDE3B is multisite phosphorylated in response to both insulin and catecholamines. We were able to identify six phosphorylation sites on PDE3B namely; 273, S296, S421, S424/5, S474 and S536. From the studies on PDE3B localization we conclude that PDE3B is localized to caveolae and endoplasmic reticulum (ER) in adipocytes and that caveolae localized PDE3B is specifically activated by catecholamines while PDE3B in ER is specifically activated by insulin. Finally, the studies on PDE3B interactions demonstrate that insulin and catecholamines stimulate the recruitment of PDE3B into large macromolecular complexes in adipocytes. The recruitment is dependent on caveolin-1 especially in response to insulin and the constituents of the PDE3B macromolecular complexes are dependent on the stimuli used. After insulin stimulation insulin signaling molecules such as protein kinase B (PKB) are associated with PDE3B in the large complex while after catecholamine stimulation adrenergic signaling molecules such as protein kinase A (PKA) are associated with PDE3B.

Details

Authors
  • Rebecka Lindh
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes

Keywords

  • secreting systems, diabetology, Endokrinologi, Endocrinology, 'caveolae' 'localization', 'phosphorylation' 'interactions', 'PDE3B' 'adipocyte' 'adipose tissue' 'diabetes' 'cAMP' 'insulin', 'lipolysis' 'caveolin-1', sekretion, diabetologi
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2007 Sep 28
Publisher
  • Lund University, Medical Faculty, Department of Experimental Medical Science
Print ISBNs978-91-85559-98-5
Publication statusPublished - 2007
Publication categoryResearch

Bibliographic note

Defence details Date: 2007-09-28 Time: 09:15 Place: Wallenberg neurocentrum, Sölvegatan 17, Lund, Segerfalksalen External reviewer(s) Name: Welsh, Michael Title: professor Affiliation: Uppsala University, BMC, Box 571, 751 23 UPPSALA ---

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