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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 12 4139-4143
Copyright © 1997 by The Endocrine Society


Original Studies

Isoproterenol and Somatostatin Decrease Plasma Leptin in Humans: A Novel Mechanism Regulating Leptin Secretion1

William T. Donahoo, Dalan R. Jensen, Trudy J. Yost and Robert H. Eckel

Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Health Sciences Center, Denver, Colorado, 80262

Address all correspondence and requests for reprints to: Robert H. Eckel, Box B-151, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, Colorado 80262. E-mail: robert.eckel{at}uchsc.edu

In cultured adipocytes, leptin is increased by insulin and decreased by cAMP. In animal models, insulin and agents that increase intracellular cAMP have been shown to similarly affect plasma leptin in vivo. This study was undertaken to test the hypothesis that in humans increased cAMP induced by isoproterenol would decrease leptin. Five groups of normal weight subjects were studied: 1) subjects infused with isoproterenol at a rate of 24 ng/kg/min (ISO24); 2) subjects infused with isoproterenol at a rate of 8 ng/kg/min (ISO8); 3) subjects infused with somatostatin/insulin/GH followed by coinfusion with 8 ng/kg/min isoproterenol (ISO8 + SRIH); 4) subjects infused with somatostatin/insulin/GH alone (SRIH); and 5) control subjects infused with saline (NS). ISO24 infusion resulted in a 27% decrease in plasma leptin over 120 min. ISO24 also increased plasma insulin over the infusion. ISO8 resulted in a 16% decrease in leptin. Saline did not change leptin. SRIH alone decreased leptin 19% over the first 120 min, however no additional fall was seen over the next 120 min the SRIH group. Nonetheless, the addition of 8 ng/kg/min ISO during the second 120 min (ISO8 + SRIH) caused a 15% further decline in plasma leptin. Therefore both isoproterenol and somatostatin reduce plasma leptin in humans. The effect of isoproterenol is likely mediated by ß-adrenergic receptors, whereas the effect of somatostatin suggests a novel mechanism for the regulation of leptin.




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