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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

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 9

Alterations in insulin-signaling components in livers from Pde3b-KO mice.

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Alterations in insulin-signaling components in livers from Pde3b-KO mice...
Western blots of liver lysates (50 μg protein/lane) were performed as described in Methods. n = 4 fed, 3 fasted mice per group. Data from an identical group of nonfasted (n = 4) and 6-hour-fasted (n = 3) WT and KO mice were similar. (A) Immunodetection with anti-phosphotyrosine (pY), anti–IRS-1, anti–insulin receptor (IR), anti–phospho-PKB, anti-PKB, anti–phospho-FKHRL1 (pS253), anti-FKHRL1, anti–phospho–GSK-3 (pY216), and anti–GSK-3 antibodies. (B) Immunodetection with anti–phospho–IRS-1 (pS612), anti–phospho–IRS-1 (pS307), anti–phospho-JNK, anti-JNK, anti–phospho-ERK, and anti-ERK antibodies.

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

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