Phosphodiesterase 3B is localized in caveolae and smooth ER in mouse hepatocytes and is important in the regulation of glucose and lipid metabolism.
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.
Berger
Karin
K
Department of Experimental Medical Sciences, Lund University, BMC C11, Lund, Sweden. karin.berger@med.lu.se
Lindh
Rebecka
R
Wierup
Nils
N
Zmuda-Trzebiatowska
Emilia
E
Lindqvist
Andreas
A
Manganiello
Vincent C
VC
Degerman
Eva
E
D000818:Animals; D021941:Caveolae / Q000201:enzymology*; D002784:Cholesterol / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000032:analysis / Q000378:metabolism*; D018871:Endoplasmic Reticulum, Smooth / Q000201:enzymology*; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism*; D050356:Lipid Metabolism; D053858:Metabolic Networks and Pathways; D051379:Mice; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D002784:Cholesterol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D005947:Glucose