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Endocrinology, doi:10.1210/en.2003-0364
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Endocrinology Vol. 144, No. 12 5293-5299
Copyright © 2003 by The Endocrine Society

Dual Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and Isoproterenol on Lipid Metabolism and Signaling in Primary Rat Adipocytes

Lina Åkesson, Bo Ahrén, Vincent C. Manganiello, Lena Stenson Holst, Gudrun Edgren and Eva Degerman

Section for Molecular Signaling, Department of Cell and Molecular Biology (L.A., L.S.H., G.E., E.D.), Department of Medicine (B.A.), Lund University, SE-221 84 Lund, Sweden; and Pulmonary-Critical Care Medicine Branch (V.C.M.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Lina Åkesson, Biomedical Center C11, SE-221 84 Lund, Sweden. E-mail: lina.akesson{at}medkem.lu.se.

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide that exerts its effects throughout the body by elevating the intracellular amounts of cAMP. In adipocytes, an increased amount of cAMP is associated with increased lipolysis. In this work we evaluated the effects of PACAP38 on triglyceride metabolism in primary rat adipocytes. Stimulation of adipocytes with PACAP (0.1–100 nM) resulted in stimulation of lipolysis to the same extent as isoproterenol. Lipolysis was blocked by 25 µM of the protein kinase A inhibitor H-89 and potentiated in the presence of 10 µM OPC3911, a phosphodiesterase 3 inhibitor. In addition, PACAP38 induced activation of protein kinase A. Insulin efficiently inhibited PACAP38-induced lipolysis in a phosphatidyl inositol 3-kinase and phosphodiesterase 3-dependent manner. Interestingly, we also found that PACAP38, as well as isoproterenol, induced potentiation of lipogenesis in the presence of insulin. These results show that PACAP38 and isoproterenol mediate catabolic as well as anabolic effects in adipocytes, depending on the concentration of insulin present. We speculate that in the early postprandial state and during fasting, when insulin levels are low, PACAP and ß-adrenergic catecholamines induce lipolysis, whereas when higher levels of insulin are present, these agents potentiate the anabolic effect of insulin, i.e. storage of triglycerides.




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L. Akesson, B. Ahren, G. Edgren, and E. Degerman
VPAC2-R Mediates the Lipolytic Effects of Pituitary Adenylate Cyclase-Activating Polypeptide/Vasoactive Intestinal Polypeptide in Primary Rat Adipocytes
Endocrinology, February 1, 2005; 146(2): 744 - 750.
[Abstract] [Full Text] [PDF]




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