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 RIS Download
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