Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Steinberg, D., Mayer, S.E., Khoo, J. C., Miller, E.A., Friedholm, B., and Eichner, R. (1975) Adv. Cyclic Nucleotide Res., 5, 549–568.
Sutherland, E.W. (1971) Cyclic AMP, Academic Press, New York, pp. 5–17.
Salzman, E.W., and Weisinberger, H. (1972) Adv. Cyclic Nucleotide Res. 1, 231–248.
Colucci, W.S., Wright, R.F., and Braunwald, E. (1986) New Engl. J. Med., 314, 290–299, 349–358.
Kramer, G.L., and Hardman, J.G. (1980) Handbook of Physiology: The Cardiovascular System II, American Physiological Society, Bethesda, MD pp. 179–199.
Stralfors, P., Bjorgell, P., and Belfrage, P. (1984) Proc. Natl. Acad. Sci. U.S.A., 81, 3317–3321.
Holm, C, Kirchgessner, T.G., Svenson, K.L., Fredrickson, G., Nelsson, S., Miller, C.G., Shively, J.E., Heinzmann, C., Sparkes, R.S., Mohandas, T., Lusis, A.J., Belfrage, P., and Schotz, M.C. (1988) Science, 241, 1503–1506.
Belfrage, P., Fredrickson, G., Olsson, H., and Stralfors, P. (1983) The Adipocyte and Obesity: Cellular and Molecular Mechanisms, Raven Press, New York, pp. 217–224.
Londos, C., Honnor, R.C., and Dhillon, G.S. (1985) J. Biol. Chem. 260. 15139–15145.
Butcher, R.W., Sneyd, J., Parks, C.R., and Sutherland, E.W. (1966) J. Biol. Chem., 241, 1651–1653.
Soderling, T.R., Corbin, J.D., and Park, C.R. (1973) J. Biol. Chem., 248, 1822–1829.
Manganiello, V.C., Smith, C.J., Degerman, E., and Belfrage, P. (1990) Cyclic Nucleotide Phosphodiesterases: Structure, Regulation, and Drug Action, John Wiley and Sons Ltd., Chichester, pp. 87–116.
Smith, C.J., and Manganiello, V.C. (1989) Mol. Pharm., 35, 381–386.
Degerman, E., Smith, C.J., Tornqvist, H., Vasta, V., Belfrage, P., and Manganiello, V.C. (1990) Proc. Natl. Acad. Sci. U.S.A., 87, 533–537.
Beavo, J. (1990) Cyclic Nucleotide Phosphodiesterases: Structure, Regulation, and Drug Action, John Wiley and Sons Ltd., Chichester, pp. 3–19.
Beavo, J. (1988) Adv. Second Messenger Phosphoprotein Res., 22, 1–38.
Weishaar, R.E., Carn, M.H., and Bristol, J.A. (1985) J. Med. Chem., 28, 537–545.
Beavo, J., and Reifsnyder, D.H. (1990) Trends in Pharmacological Sciences, 11, 150–156.
Degerman, E., Belfrage, P., Newman, A.H., Rice, K.C., and Manganiello, V.C. (1987) J. Biol. Chem., 262, 5797–5807.
Degerman, E., Manganiello, V.C., Newman, A.H., Rice, K.C., and Belfrage, P. (1988) Adv. Second Messengers and Phosphoproteins, 12, 171–182.
Rascon, A., Belfrage, P., Lindgren, S., Andersson, K.E., Newman, A.H., Manganiello, V.C., and Degerman, E. (1990) Purine Nucleosides and Nucleotides in Cell Signalling: Targets for New Drugs, Springer-Verlag, New York, pp. 353–358.
Kono, T., Robinson, F.W., and Sarver, J.A. (1975) J. Biol. Chem., 250. 7826–7835.
Kauffman, R.F., Crowe, V.G., Utterback, B.G., and Robertson, D.W. (1987) Mol. Pharm., 30, 609–616.
Masuoka, H., Ito, M., Nakano, T., Naka, M., and Tanaka, T. (1990) J. Cardiovasc. Pharm., 15, 302–307.
Grant, P.W., and Colman, R.W. (1984) Biochemistry, 23, 1801–1807.
Harrison, S.A., Reifsnyder, D.H., Gallis, B., Cadd, C.G., and Beavo, J.A. (1986) Mol. Pharm., 25, 506–514.
Macphee, C.H., Harrison, S.A., and Beavo, J.A. (1986) Proc. Natl. Acad. Sci. U.S.A., 83, 6660–6663.
Boyes, S., and Loten, E.G. (1988) Eur. J. Biochem., 174, 303–309.
Houslay, M.D., and Kilgour, E. (1990) Cyclic Nucleotide Phosphodiesterases: Structure, Regulation, and Drug Action, John Wiley and Sons, Ltd., Chichester, pp. 185–226.
Macphee, C.H., Reifsnyder, D.H., Moore, T.A., Levea, K.M., and Beavo, J.A. (1988) J. Biol. Chem., 263, 10353–10358.
Grant, P.H., Marinaro, A.F., and Colman, R.W. (1988) Proc. Natl. Acad. Sci. U.S.A., 85, 9071–9075.
Smith, C.J., Vasta V., Degerman, E., Tornqvist, H., and Manganiello, V.C., ms. submitted.
Reeves, M.L., and England, P.J. (1990) Cyclic Nucleotide Phosphodiesterases: Structure, Regulation, and Drug Action, John Wiley and Sons Ltd., Chichester, pp. 299–316.
Lindgren, S., Rascon, A., Andersson, K.-E., Manganiello, V.C., and Degerman, E. (1990) ms. submitted.
Alvarez, R., Banerjie, G.L., Brunz, J.J., Jones, G.L., Littachwager, K., Strossberg, A., and Venuti, M.C. (1986) Mol. Pharm., 29, 554–560.
Gettys, T.W., Vine, A.J., Simonds, M.F., and Corbin, J.D. (1988) J. Biol. Chem., 263, 10359–10363.
Beebe, S.J., Redman, J.B., Blackmore, P.W., and Corbin, J.D. (1985) J. Biol. Chem., 260, 15781–15788.
Goswami, A., and Rosenberg, I. (1985) J. Biol. Chem., 260, 82–85.
Hepp, K.O., and Renner, R. (1972) FEBS Lett., 20, 191–194.
Low, M.G., and Saltiel, A.R. (1988) Science, 239, 268–275.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
Manganiello, V.C., Smith, C.J., Degerman, E., Vasta, V., Tornqvist, H., Belfrage, P. (1991). Molecular Mechanisms Involved in the Antilipolytic Action of Insulin: Phosphorylation and Activation of a Particulate Adipocyte cAMP Phosphodiesterase. In: Raizada, M.K., LeRoith, D. (eds) Molecular Biology and Physiology of Insulin and Insulin-Like Growth Factors. Advances in Experimental Medicine and Biology, vol 293. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5949-4_22
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5949-4_22
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5951-7
Online ISBN: 978-1-4684-5949-4
eBook Packages: Springer Book Archive