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

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 lipogenesis, 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.

Pubmed ID: 17143332

Authors

  • Choi YH
  • Park S
  • Hockman S
  • Zmuda-Trzebiatowska E
  • Svennelid F
  • Haluzik M
  • Gavrilova O
  • Ahmad F
  • Pepin L
  • Napolitano M
  • Taira M
  • Sundler F
  • Stenson Holst L
  • Degerman E
  • Manganiello VC

Journal

The Journal of clinical investigation

Publication Data

December 4, 2006

Associated Grants

None

Mesh Terms

  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Adipocytes
  • Adiponectin
  • Animals
  • Blotting, Western
  • Catecholamines
  • Cyclic AMP
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Energy Metabolism
  • Female
  • Homeostasis
  • Immunohistochemistry
  • Insulin
  • Insulin Resistance
  • Islets of Langerhans
  • Lipolysis
  • Liver
  • Male
  • Mice
  • Mice, Knockout
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Triglycerides