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

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Author

  • Emilia Zmuda-Trzebiatowska
  • Alina Oknianska
  • Vincent Manganiello
  • Eva Degerman

Summary, in English

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.

Publishing year

2006

Language

English

Pages

382-390

Publication/Series

Cellular Signalling

Volume

18

Issue

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Microbiology

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

Status

Published

Research group

  • Insulin Signal Transduction

ISBN/ISSN/Other

  • ISSN: 1873-3913