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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • 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
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinska grundvetenskaper
Originalspråkengelska
Sidor (från-till)3240-3251
TidskriftJournal of Clinical Investigation
Volym116
Utgivningsnummer12
StatusPublished - 2006
PublikationskategoriForskning
Peer review utfördJa