Donahoo W T, Jensen D R, Yost T J, Eckel R H
Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Health Sciences Center, Denver 80262, USA.
J Clin Endocrinol Metab. 1997 Dec;82(12):4139-43. doi: 10.1210/jcem.82.12.4434.
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 beta-adrenergic receptors, whereas the effect of somatostatin suggests a novel mechanism for the regulation of leptin.
在培养的脂肪细胞中，瘦素水平受胰岛素升高而受环磷酸腺苷（cAMP）降低。在动物模型中，胰岛素及能升高细胞内cAMP的药物在体内同样会影响血浆瘦素水平。本研究旨在验证异丙肾上腺素诱导的cAMP升高会降低人体瘦素水平这一假说。研究了五组正常体重受试者：1）以24 ng/kg/min的速率输注异丙肾上腺素的受试者（ISO24）；2）以8 ng/kg/min的速率输注异丙肾上腺素的受试者（ISO8）；3）先输注生长抑素/胰岛素/生长激素，随后以8 ng/kg/min的速率联合输注异丙肾上腺素的受试者（ISO8 + SRIH）；4）单独输注生长抑素/胰岛素/生长激素的受试者（SRIH）；5）输注生理盐水的对照受试者（NS）。ISO24输注导致120分钟内血浆瘦素降低27%。ISO24输注期间还使血浆胰岛素升高。ISO8使瘦素降低16%。生理盐水未改变瘦素水平。单独的SRIH在最初120分钟内使瘦素降低19%，然而在接下来的120分钟内SRIH组未观察到进一步下降。尽管如此，在第二个120分钟内添加8 ng/kg/min的ISO（ISO8 + SRIH）使血浆瘦素进一步下降15%。因此，异丙肾上腺素和生长抑素均可降低人体血浆瘦素水平。异丙肾上腺素的作用可能由β - 肾上腺素能受体介导，而生长抑素的作用提示了一种调节瘦素的新机制。
