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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 Article has an altmetric score of 7

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

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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 11

Adiponectin expression.

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Adiponectin expression.
(A and B) Serum adiponectin concentrations were ...
(A and B) Serum adiponectin concentrations were quantified in WT and KO mice, either fed or after fasting for 20 hours, fed normal chow (A; 6 months of age) or at the start (at 2 months of age) and end (after 14 weeks) of a 60%-fat diet (B). Data (mean ± SEM; n = 6–9 mice per group) were similar in 2 other experiments for A. (C) Adiponectin mRNA from epidydimal fat pads was amplified via real-time quantitative RT-PCR of total RNA as described in Supplemental Methods. Data (mean ± SEM; n = 4 mice per group) were similar in 2 other experiments. Inset: Agarose gel electrophoresis of adiponectin real-time RT-PCR products. A, adiponectin; C, cyclophilin A. Data from 1 other experiment were similar. (D) At the indicated times after i.p. injection (10 ml/kg) of CL (1.0 mg/kg) in PBS or PBS alone administered to 4- to 5-month old WT and KO mice, serum adiponectin levels were measured. Data (mean ± SEM) represent the percent change relative to basal values at time 0 (n = 4–9 mice per group). Basal adiponectin values were 22.2 ± 0.7 and 41.0 ± 2.0 μg/ml in WT and KO, respectively. Note: Values at every time point following CL injection were significantly lower (P < 0.01) except at 10 minutes in KO mice in the case of adiponectin. Data from 1 other experiment were similar. *P < 0.05; **P < 0.01.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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