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

Choi, Young Hun; Park, Sunhee; Hockman, Steven; Zmuda-Trzebiatowska, Emilia; Svennelid, Fredrik LU ; Haluzik, Martin; Gavrilova, Oksana; Ahmad, Faiyaz; Pepin, Laurent and Napolitano, Maria, et al. (2006) In Journal of Clinical Investigation 116(12). p.3240-3251
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... (More)
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. (Less)
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Journal of Clinical Investigation
volume
116
issue
12
pages
3240 - 3251
publisher
The Journal of Clinical Investigation
external identifiers
  • wos:000242606900023
  • scopus:33845348168
ISSN
0021-9738
DOI
10.1172/JCI24867
language
English
LU publication?
yes
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c33cfbd3-0a56-4a90-a485-5091051caa1c (old id 683632)
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2007-12-21 12:45:56
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2018-10-14 04:05:51
@article{c33cfbd3-0a56-4a90-a485-5091051caa1c,
  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.},
  author       = {Choi, Young Hun and Park, Sunhee and Hockman, Steven and Zmuda-Trzebiatowska, Emilia and Svennelid, Fredrik and Haluzik, Martin and Gavrilova, Oksana and Ahmad, Faiyaz and Pepin, Laurent and Napolitano, Maria and Taira, Masato and Sundler, Frank and Stenson, Lena and Degerman, Eva and Manganiello, Vincent C.},
  issn         = {0021-9738},
  language     = {eng},
  number       = {12},
  pages        = {3240--3251},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice},
  url          = {http://dx.doi.org/10.1172/JCI24867},
  volume       = {116},
  year         = {2006},
}