title: The Role of PDE3B Phosphorylation in the Inhibition of Lipolysis by Insulin.
abstract: Inhibition of adipocyte lipolysis by insulin is important for whole-body energy homeostasis; its disruption has been implicated as contributing to the development of insulin resistance and type 2 diabetes mellitus. The main target of the antilipolytic action of insulin is believed to be phosphodiesterase 3B (PDE3B), whose phosphorylation by Akt leads to accelerated degradation of the prolipolytic second messenger cyclic AMP (cAMP). To test this hypothesis genetically, brown adipocytes lacking PDE3B were examined for their regulation of lipolysis. In Pde3b knockout (KO) adipocytes, insulin was unable to suppress β-adrenergic receptor-stimulated glycerol release. Reexpressing wild-type PDE3B in KO adipocytes fully rescued the action of insulin against lipolysis. Surprisingly, a mutant form of PDE3B that ablates the major Akt phosphorylation site, murine S273, also restored the ability of insulin to suppress lipolysis. Taken together, these data suggest that phosphorylation of PDE3B by Akt is not required for insulin to suppress adipocyte lipolysis.
authors.affiliation: Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DiPilato
authors.affiliation: Cardiovascular and Pulmonary Branch, The National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Faiyaz
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Harms
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Seale
authors.affiliation: Cardiovascular and Pulmonary Branch, The National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Manganiello
authors.affiliation: Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA birnbaum@mail.med.upenn.edu.
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Birnbaum
mesh_terms: D041721:3T3-L1 Cells; D052437:Adipocytes, Brown / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D055786:Gene Knockout Techniques; D005990:Glycerol / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008066:Lipolysis; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D007328:Insulin; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D005990:Glycerol