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Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes.

Zmuda-Trzebiatowska, Emilia LU ; Oknianska, Alina LU ; Manganiello, Vincent and Degerman, Eva LU (2006) In Cellular Signalling 18(3). p.382-390
Abstract
In adipocytes, phosphorylation and activation of PDE3B is a key event in the antilipolytic action of insulin. The role of PDE4, another PDE present in adipocytes, is not yet known. In this work we investigate the role of PDE3B and PDE4 in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis. Inhibition of PDE3 (OPC3911, milrinone) but not PDE4 (RO 20-1724) lowered insulin-induced glucose uptake and lipogenesis, especially in the presence of isoproterenol (a general beta-adrenergic agonist), CL316243, a selective beta 3-adrenergic agonist, and pituitary adenylate cyclase-activating peptide. The inhibitory effect of OPC3911 was associated with reduced translocation of GLUT-4 from the cytosol to the plasma membrane. Both... (More)
In adipocytes, phosphorylation and activation of PDE3B is a key event in the antilipolytic action of insulin. The role of PDE4, another PDE present in adipocytes, is not yet known. In this work we investigate the role of PDE3B and PDE4 in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis. Inhibition of PDE3 (OPC3911, milrinone) but not PDE4 (RO 20-1724) lowered insulin-induced glucose uptake and lipogenesis, especially in the presence of isoproterenol (a general beta-adrenergic agonist), CL316243, a selective beta 3-adrenergic agonist, and pituitary adenylate cyclase-activating peptide. The inhibitory effect of OPC3911 was associated with reduced translocation of GLUT-4 from the cytosol to the plasma membrane. Both OPC3911 and RO 20-1724 increased protein kinase A (PKA) activity and lipolysis. H89, a PKA inhibitor, did not affect OPC3911-mediated inhibition of insulin-induced glucose uptake and lipogenesis, whereas 8-pCPT-2'-O-Me-cAMP, an Epac agonist which mediates PKA independent cAMP signaling events, mimicked all the effects of OPC3911. Insulin-mediated activation of protein kinase B, a kinase involved in insulin-induced glucose uptake, was apparently not altered by OPC3911. In summary, our data suggest that PDE3B, but not PDE4, contributes to the regulation of insulin-induced glucose uptake, GLUT-4 translocation, and lipogenesis presumably by regulation of a cAMP/Epac signalling mechanisms. (c) 2005 Elsevier Inc. All rights reserved. (Less)
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keywords
PDE3B, PDE4, Epac, GLUT-4, glucose uptake, lipogenesis, adipocyte, CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE, MEDIATED SIGNAL-TRANSDUCTION, DEPENDENT PROTEIN-KINASE, PANCREATIC BETA-CELL, ADIPOSE-CELLS, FAT-CELLS, GLUT4-CONTAINING VESICLES, CAMP-PHOSPHODIESTERASE, ANTILIPOLYTIC ACTION, TRANSPORTER GLUT4
in
Cellular Signalling
volume
18
issue
3
pages
382 - 390
publisher
Elsevier
external identifiers
  • wos:000233954800012
  • scopus:27844585184
ISSN
1873-3913
DOI
10.1016/j.cellsig.2005.05.007
language
English
LU publication?
yes
id
4d0b133f-d28d-4c4a-ae6c-94d4d78af90b (old id 139989)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15961276&query_hl=58
date added to LUP
2016-04-01 12:08:21
date last changed
2020-01-12 09:17:13
@article{4d0b133f-d28d-4c4a-ae6c-94d4d78af90b,
  abstract     = {In adipocytes, phosphorylation and activation of PDE3B is a key event in the antilipolytic action of insulin. The role of PDE4, another PDE present in adipocytes, is not yet known. In this work we investigate the role of PDE3B and PDE4 in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis. Inhibition of PDE3 (OPC3911, milrinone) but not PDE4 (RO 20-1724) lowered insulin-induced glucose uptake and lipogenesis, especially in the presence of isoproterenol (a general beta-adrenergic agonist), CL316243, a selective beta 3-adrenergic agonist, and pituitary adenylate cyclase-activating peptide. The inhibitory effect of OPC3911 was associated with reduced translocation of GLUT-4 from the cytosol to the plasma membrane. Both OPC3911 and RO 20-1724 increased protein kinase A (PKA) activity and lipolysis. H89, a PKA inhibitor, did not affect OPC3911-mediated inhibition of insulin-induced glucose uptake and lipogenesis, whereas 8-pCPT-2'-O-Me-cAMP, an Epac agonist which mediates PKA independent cAMP signaling events, mimicked all the effects of OPC3911. Insulin-mediated activation of protein kinase B, a kinase involved in insulin-induced glucose uptake, was apparently not altered by OPC3911. In summary, our data suggest that PDE3B, but not PDE4, contributes to the regulation of insulin-induced glucose uptake, GLUT-4 translocation, and lipogenesis presumably by regulation of a cAMP/Epac signalling mechanisms. (c) 2005 Elsevier Inc. All rights reserved.},
  author       = {Zmuda-Trzebiatowska, Emilia and Oknianska, Alina and Manganiello, Vincent and Degerman, Eva},
  issn         = {1873-3913},
  language     = {eng},
  number       = {3},
  pages        = {382--390},
  publisher    = {Elsevier},
  series       = {Cellular Signalling},
  title        = {Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes.},
  url          = {https://lup.lub.lu.se/search/ws/files/2797645/624752.pdf},
  doi          = {10.1016/j.cellsig.2005.05.007},
  volume       = {18},
  year         = {2006},
}