Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B–null mice
Young Hun Choi, … , Eva Degerman, Vincent C. Manganiello
Young Hun Choi, … , Eva Degerman, Vincent C. Manganiello
Published December 1, 2006
Citation Information: J Clin Invest. 2006;116(12):3240-3251. https://doi.org/10.1172/JCI24867.
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Research Article Metabolism

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

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 β 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 β3-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.

Authors

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 Holst, Eva Degerman, Vincent C. Manganiello

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Figure 7

ITTs and GTTs.

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ITTs and GTTs. (A and B) Male 5-month-old WT and KO mice were fasted ove...
(A and B) Male 5-month-old WT and KO mice were fasted overnight for 20 hours prior to i.p. injection (10 ml/kg) of insulin (0.5 U/kg) in PBS or PBS alone, and blood glucose (A) and serum FFA (B) levels were measured at the indicated times. Glucose concentrations (A) are reported relative to those at time 0. Basal glucose values in WT and KO mice were 70 ± 3 and 66 ± 3 mg/dl, respectively. Data (mean ± SEM; n = 6 mice per group) were similar in 8 (A) and 2 (B) other experiments. (C and D) Male 9-month-old WT and KO mice were fasted overnight, with free access to water. At the indicated times after i.p. injections (10 ml/kg) of PBS alone or of glucose (2 g/kg) in PBS, blood glucose (C) and serum insulin (D) levels were quantified. Data (mean ± SEM; n = 6 mice per group) were similar in 2 other experiments. *P < 0.05; **P < 0.01.