Molecular Mechanisms Involved in the Antilipolytic Action of Insulin: Phosphorylation and Activation of a Particulate Adipocyte cAMP Phosphodiesterase

  • Vincent C. Manganiello
  • Carolyn J. Smith
  • Eva Degerman
  • Valeria Vasta
  • Hans Tornqvist
  • Per Belfrage
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 293)


cAMP is an important intracellular second messenger in hormonal regulation of many physiological processes, including lipolysis, glycogenolysis, platelet aggregation, myocardial contractility, and smooth muscle relaxation (1–5). The isolated rat adipocyte has served as a useful model system in which to study hormonal and cAMP-mediated regulation of lipolysis. As outlined in Fig. 1, in rat adipocytes lipolytic hormones (e.g., catecholamines, glucagon, ACTH) and certain antilipolytic effectors (such as adenosine and prostaglandin E1) interact with specific cell surface receptors and transmit stimulatory or inhibitory signals to the catalytic unit of adenylate cyclase via stimulatory or inhibitory guanyl nucleotide binding proteins, respectively. cAMP activates cAMP-dependent protein kinase (cAMP-PrK) which phosphorylates, on serine-563 (6,7), and activates the hormone-sensitive lipase, leading to hydrolysis of stored triglyceride with release of glycerol and free fatty acids. Steady state concentrations of cAMP are also regulated by cyclic nucleotide phosphodiesterases, enzymes that catalyze hydrolysis of cAMP to 5’AMP. From the scheme presented in Fig. 1, it is obvious that lipolysis can be regulated at several loci, i.e., at the level of cAMP formation or destruction, cAMP-PrK, protein phosphatase(s), etc.


Adenosine Deaminase Smooth Muscle Relaxation Cyclic Nucleotide Phosphodiesterase cAMP Analog Triglyceride Lipase 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Vincent C. Manganiello
    • 1
  • Carolyn J. Smith
    • 1
  • Eva Degerman
    • 2
  • Valeria Vasta
    • 3
  • Hans Tornqvist
    • 2
  • Per Belfrage
    • 2
  1. 1.Laboratory of Cellular Metabolism, National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Department of BiochemistryUniversity of FlorenceFlorenceItaly
  3. 3.Department of Medical and Physiological ChemistryUniversity of LundLundSweden

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