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Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice

Author:
  • Young Hun Choi
  • Sunhee Park
  • Steven Hockman
  • Emilia Zmuda-Trzebiatowska
  • Fredrik Svennelid
  • Martin Haluzik
  • Oksana Gavrilova
  • Faiyaz Ahmad
  • Laurent Pepin
  • Maria Napolitano
  • Masato Taira
  • Frank Sundler
  • Lena Stenson
  • Eva Degerman
  • Vincent C. Manganiello
Publishing year: 2006
Language: English
Pages: 3240-3251
Publication/Series: Journal of Clinical Investigation
Volume: 116
Issue: 12
Document type: Journal article
Publisher: The Journal of Clinical Investigation

Abstract english

Cyclic nucleotide phosphodiesterase 3B (PDE3B) has been suggested to be critical for mediating insulin/IGF-1 inhibition of cAMP signaling in adipocytes, liver, and pancreatic beta cells. In Pde3b-KO adipocytes we found decreased adipocyte size, unchanged insulin-stimulated phosphorylation of protein kinase B and activation of glucose uptake, enhanced catecholamine-stimulated lipolysis and insulin-stimulated hpogenesis, and blocked insulin inhibition of catecholamine-stimulated lipolysis. Glucose, alone or in combination with glucagon-like peptide-1, increased insulin secretion more in isolated pancreatic KO islets, although islet size and morphology and immunoreactive insulin and glucagon levels were unchanged. The beta(3)-adrenergic agonist CL 316,243 (CL) increased lipolysis and serum insulin more in KO mice, but blood glucose reduction was less in CL-treated KO mice. Insulin resistance was observed in KO mice, with liver an important site of alterations in insulin-sensitive glucose production. In KO mice, liver triglyceride and cAMP contents were increased, and the liver content and phosphorylation states of several insulin signaling, gluconeogenic, and inflammation- and stress-related components were altered. Thus, PDE3B may be important in regulating certain cAMP signaling pathways, including lipolysis, insulin-induced antilipolysis, and cAMP-mediated insulin secretion. Altered expression and/or regulation of PDE3B may contribute to metabolic dysregulation, including systemic insulin resistance.

Keywords

  • Basic Medicine

Other

Published
  • Insulin Signal Transduction
  • ISSN: 0021-9738
Eva Degerman
E-mail: eva [dot] degerman [at] med [dot] lu [dot] se

Professor

Insulin Signal Transduction

+46 46 222 85 83

+46 70 885 83 62

BMC C1121b

66

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