The role of phosphodiesterase 3B in energy metabolism

Emilia Zmuda-Trzebiatowska

The role of phosphodiesterase 3B in energy metabolism

Emilia Zmuda-Trzebiatowska

Insulin Signal Transduction

Research output: Thesis › Doctoral Thesis (compilation)

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.

Original language	English
Qualification	Doctor
Awarding Institution	Department of Experimental Medical Science
Supervisors/Advisors	Degerman, Eva, Supervisor
Award date	2007 Apr 27
Publisher	Lund University: Faculty of Medicine
ISBN (Print)	978-91-85559-55-8
Publication status	Published - 2007

Bibliographical note

Defence details

Date: 2007-04-27
Time: 09:15
Place: Segerfalkssalen, Wallenberg Neurocentrum, Sölvegatan 17, Lund

External reviewer(s)

Name: Bengtsson, Tore
Title: Docent
Affiliation: Wenner-Gren Institutet, University of Stockholm

---

<div class="article_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.</div>
<div class="article_info">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.</div>
<div class="article_info">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.</div>
<div class="article_info">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.</div>

Subject classification (UKÄ)

Basic Medicine

Free 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

@phdthesis{661132c1d8d5472bb14f2c249c25db01,

title = "The role of phosphodiesterase 3B in energy metabolism",

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.",

keywords = "diabetology, secreting systems, Endocrinology, Physiology, Fysiologi, Medicin (m{\"a}nniska och djur), glucose uptake, lipogenesis, adipocyte, Medicine (human and vertebrates), cAMP, PDE3B, insulin, Endokrinologi, sekretion, diabetologi",

author = "Emilia Zmuda-Trzebiatowska",

note = "Defence details Date: 2007-04-27 Time: 09:15 Place: Segerfalkssalen, Wallenberg Neurocentrum, S{\"o}lvegatan 17, Lund External reviewer(s) Name: Bengtsson, Tore Title: Docent Affiliation: Wenner-Gren Institutet, University of Stockholm --- <div class={"}article_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.</div> <div class={"}article_info{"}>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.</div> <div class={"}article_info{"}>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.</div> <div class={"}article_info{"}>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.</div>",

year = "2007",

language = "English",

isbn = "978-91-85559-55-8",

series = "Faculty of Medicine Doctoral Dissertation Series",

publisher = "Lund University: Faculty of Medicine",

type = "Doctoral Thesis (compilation)",

school = "Department of Experimental Medical Science",

}

TY - THES

T1 - The role of phosphodiesterase 3B in energy metabolism

AU - Zmuda-Trzebiatowska, Emilia

N1 - Defence details Date: 2007-04-27 Time: 09:15 Place: Segerfalkssalen, Wallenberg Neurocentrum, Sölvegatan 17, Lund External reviewer(s) Name: Bengtsson, Tore Title: Docent Affiliation: Wenner-Gren Institutet, University of Stockholm --- <div class="article_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.</div> <div class="article_info">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.</div> <div class="article_info">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.</div> <div class="article_info">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.</div>

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - diabetology

KW - secreting systems

KW - Endocrinology

KW - Physiology

KW - Fysiologi

KW - Medicin (människa och djur)

KW - glucose uptake

KW - lipogenesis

KW - adipocyte

KW - Medicine (human and vertebrates)

KW - cAMP

KW - PDE3B

KW - insulin

KW - Endokrinologi

KW - sekretion

KW - diabetologi

M3 - Doctoral Thesis (compilation)

SN - 978-91-85559-55-8

T3 - Faculty of Medicine Doctoral Dissertation Series

PB - Lund University: Faculty of Medicine

ER -

The role of phosphodiesterase 3B in energy metabolism

Abstract

Bibliographical note

Subject classification (UKÄ)

Free keywords

UN SDGs

Fingerprint

Cite this