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The role of phosphodiesterase 3B in energy metabolism

Zmuda-Trzebiatowska, Emilia LU (2007) In Faculty of Medicine Doctoral Dissertation Series
Abstract
Energy metabolism at the level of any particular tissue is tightly regulated by hormones, neurotransmitters and cytokines in order to maintain overall energy homeostasis. Any dysfunctions in energy metabolism may lead to more or less severe consequences, with obesity and type 2 diabetes being the most prevalent ones. Type 2 diabetes is characterized by defective insulin secretion (?-cell dysfunction) and action (insulin resistance). The cAMP-degrading enzyme, PDE3B mediates antilipolytic insulin action in adipocytes and antiglycogenolytic insulin action in hepatocytes. The aim of this work was to evaluate the role of PDE3B in overall energy homeostasis as well as in insulin-induced glucose uptake and lipogenesis in adipocytes. Furthermore,... (More)
Energy metabolism at the level of any particular tissue is tightly regulated by hormones, neurotransmitters and cytokines in order to maintain overall energy homeostasis. Any dysfunctions in energy metabolism may lead to more or less severe consequences, with obesity and type 2 diabetes being the most prevalent ones. Type 2 diabetes is characterized by defective insulin secretion (?-cell dysfunction) and action (insulin resistance). The cAMP-degrading enzyme, PDE3B mediates antilipolytic insulin action in adipocytes and antiglycogenolytic insulin action in hepatocytes. The aim of this work was to evaluate the role of PDE3B in overall energy homeostasis as well as in insulin-induced glucose uptake and lipogenesis in adipocytes. Furthermore, we investigated mechanisms whereby PDE3B could regulate energy metabolism as well as long-term regulation of the enzyme by insulin and catecholamines. Used models included PDE3B KO mice generated for the first time, primary adipocytes and cell lines. The results indicate that PDE3B plays unique roles in adipocytes, liver and pancreatic ?-cells, and is crucial for the regulation of overall energy metabolism. Furthermore, in adipocyes, PDE3B is involved in the regulation of insulin-induced glucose uptake and lipogenesis, presumably via regulation of cAMP/Epac signalling which has an impact on phosphorylation and activation of PKB and ACC. At last, in adipocytes PDE3B and PDE4 are regulated by insulin and catecholamines also on a long-term basis. Altered expression of adipocyte PDEs by insulin and catecholamines may contribute to altered regulation of metabolism in obesity and diabetic states. (Less)
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author
supervisor
opponent
  • Docent Bengtsson, Tore, Wenner-Gren Institutet, University of Stockholm
organization
publishing date
type
Thesis
publication status
published
subject
keywords
diabetology, secreting systems, Endocrinology, Physiology, Fysiologi, Medicin (människa och djur), glucose uptake, lipogenesis, adipocyte, Medicine (human and vertebrates), cAMP, PDE3B, insulin, Endokrinologi, sekretion, diabetologi
in
Faculty of Medicine Doctoral Dissertation Series
pages
120 pages
publisher
Lund University: Faculty of Medicine
defense location
Segerfalkssalen, Wallenberg Neurocentrum, Sölvegatan 17, Lund
defense date
2007-04-27 09:15:00
ISSN
1652-8220
ISBN
978-91-85559-55-8
language
English
LU publication?
yes
additional info
Y Choi, S Park, S Hockman, E Zmuda-Trzebiatowska, F Svennelid, M Haluzik, O Gavrilova, L Peppin, M Napolitano, M Taira, F Ahmad, LS Holst, E Degerman and V Manganiello. 2006. Alterations in regulation of energy homeostasis in Cyclic Nucleotide Phosphodiesterase 3BNull Mice. Journal of Clinical Investigations, vol 116 pp 3240-3251.
E Zmuda-Trzebiatowska, A Oknianska, V Manganiello and E Degerman. 2006. Role of PDE 3 in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes. Cellular Signalling, vol 18 pp 382-390.
E Zmuda-Trzebiatowska, V Manganiello and E Degerman. 2007. Novel mechanisms of the regulation of Protein kinase B in adipocytes; Implications for Protein kinase A, Epac, Phosphodiesterases 3 and 4. Cellular Signalling, vol 19 pp 81-86.
A Oknianska, E Zmuda-Trzebiatowska, V Manganiello and E Degerman. 2007. Long-term regulation of cyclic nucleotide phosphodiesterase type 3B and 4 in 3T3-L1 adipocytes. Biochem Biophys Res Commun., vol 23;353 pp 1080-1085.
id
661132c1-d8d5-472b-b14f-2c249c25db01 (old id 548316)
date added to LUP
2016-04-01 15:43:40
date last changed
2019-11-19 13:49:55
@phdthesis{661132c1-d8d5-472b-b14f-2c249c25db01,
  abstract     = {{Energy metabolism at the level of any particular tissue is tightly regulated by hormones, neurotransmitters and cytokines in order to maintain overall energy homeostasis. Any dysfunctions in energy metabolism may lead to more or less severe consequences, with obesity and type 2 diabetes being the most prevalent ones. Type 2 diabetes is characterized by defective insulin secretion (?-cell dysfunction) and action (insulin resistance). The cAMP-degrading enzyme, PDE3B mediates antilipolytic insulin action in adipocytes and antiglycogenolytic insulin action in hepatocytes. The aim of this work was to evaluate the role of PDE3B in overall energy homeostasis as well as in insulin-induced glucose uptake and lipogenesis in adipocytes. Furthermore, we investigated mechanisms whereby PDE3B could regulate energy metabolism as well as long-term regulation of the enzyme by insulin and catecholamines. Used models included PDE3B KO mice generated for the first time, primary adipocytes and cell lines. The results indicate that PDE3B plays unique roles in adipocytes, liver and pancreatic ?-cells, and is crucial for the regulation of overall energy metabolism. Furthermore, in adipocyes, PDE3B is involved in the regulation of insulin-induced glucose uptake and lipogenesis, presumably via regulation of cAMP/Epac signalling which has an impact on phosphorylation and activation of PKB and ACC. At last, in adipocytes PDE3B and PDE4 are regulated by insulin and catecholamines also on a long-term basis. Altered expression of adipocyte PDEs by insulin and catecholamines may contribute to altered regulation of metabolism in obesity and diabetic states.}},
  author       = {{Zmuda-Trzebiatowska, Emilia}},
  isbn         = {{978-91-85559-55-8}},
  issn         = {{1652-8220}},
  keywords     = {{diabetology; secreting systems; Endocrinology; Physiology; Fysiologi; Medicin (människa och djur); glucose uptake; lipogenesis; adipocyte; Medicine (human and vertebrates); cAMP; PDE3B; insulin; Endokrinologi; sekretion; diabetologi}},
  language     = {{eng}},
  publisher    = {{Lund University: Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{The role of phosphodiesterase 3B in energy metabolism}},
  year         = {{2007}},
}