Phosphodiesterase 3B is localized in caveolae and smooth ER in mouse hepatocytes and is important in the regulation of glucose and lipid metabolism

• Published in: PloS one Vol. 4; no. 3; p. e4671
• Main Authors: Berger, Karin, Lindh, Rebecka, Wierup, Nils, Zmuda-Trzebiatowska, Emilia, Lindqvist, Andreas, Manganiello, Vincent C, Degerman, Eva
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05-03-2009; Public Library of Science (PLoS)
• Subjects: 3',5'-Cyclic-nucleotide phosphodiesterase; Adipocytes; Animals; Basic Medicine; Caveolae; Caveolae - enzymology; Caveolin; Caveolin-1; Cell and Molecular Biology; Cell Biology/Cell Signaling; Cell cycle; Cell- och molekylärbiologi; Cellular signal transduction; Cholesterol; Cholesterol - metabolism; Clinical Medicine; Coenzyme A; Cyclic adenosine monophosphate; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 3 - analysis; Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism; Diabetes; Diabetes and Endocrinology/Obesity; Diabetes and Endocrinology/Type 2 Diabetes; Diabetes mellitus; Endocrinology and Diabetes; Endokrinologi och diabetes; Endoplasmic reticulum; Endoplasmic Reticulum, Smooth - enzymology; Enzymes; Fatty liver; Gene expression; Glucose; Glucose - metabolism; Health Sciences; Hepatocytes; Hepatocytes - enzymology; Hepatocytes - metabolism; Hepatology; Homeostasis; Hälsovetenskap; Immunoglobulins; Insulin; Insulin resistance; Insulin secretion; Klinisk medicin; Laboratories; Lipid Metabolism; Lipids; Lipolysis; Liver; Localization; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Metabolic Networks and Pathways; Metabolic syndrome; Metabolism; Mice; Nutrition and Dietetics; Näringslära; Peptides; Phosphodiesterase; Phosphorylation; Physiology; Protein binding; Proteins; Reductase; Regulations; Rodents; Secretion; Signal processing; Signal transduction; Sterol regulatory element-binding protein; Sterol regulatory element-binding protein 1c; Transduction; Trends; Triglycerides; Triglycerides - metabolism; Type 2 diabetes; United States > US; Maryland; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004671

Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of signal transduction processes mediated by cAMP and cGMP. One PDE family member, PDE3B, plays an important role in the regulation of a variety of metabolic processes such as lipolysis and insulin secretion. In this study, the cellular localization and the role of PDE3B in the regulation of triglyceride, cholesterol and glucose metabolism in hepatocytes were investigated. PDE3B was identified in caveolae, specific regions in the plasma membrane, and smooth endoplasmic reticulum. In caveolin-1 knock out mice, which lack caveolae, the amount of PDE3B protein and activity were reduced indicating a role of caveolin-1/caveolae in the stabilization of enzyme protein. Hepatocytes from PDE3B knock out mice displayed increased glucose, triglyceride and cholesterol levels, which was associated with increased expression of gluconeogenic and lipogenic genes/enzymes including, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor gamma, sterol regulatory element-binding protein 1c and hydroxyl-3-methylglutaryl coenzyme A reductase. In conclusion, hepatocyte PDE3B is localized in caveolae and smooth endoplasmic reticulum and plays important roles in the regulation of glucose, triglyceride and cholesterol metabolism. Dysregulation of PDE3B could have a role in the development of fatty liver, a condition highly relevant in the context of type 2 diabetes.