ISOPROTERENOL AND SOMATOSTATIN DECREASE PLASMA LEPTIN IN HUMANS - A NOVEL MECHANISM REGULATING LEPTIN SECRETION

In cultured adipocytes, leptin is increased by insulin and decreased b y cAMP. In animal models, insulin and agents that increase intracellul ar cAMP have been shown to similarly affect plasma leptin in vivo. Thi s study was undertaken to test the hypothesis that in humans increased cAMP induced by isoproterenol would decrease leptin. Five groups of n ormal weight subjects were studied: 1) subjects infused with isoproter enol at a rate of 24 ng/kg/min (ISO24); 2) subjects infused with isopr oterenol at a rate of 8 ng/kg/min (ISO8); 3) subjects infused with som atostatin/insulin/GH followed by coinfusion with 8 ng/kg/min isoproter enol (ISO8 + SRIH); 4) subjects infused with somatostatin/insulin/GH a lone (SRIH); and 5) control subjects infused with saline (NS). ISO24 i nfusion resulted in a 27% decrease in plasma leptin over 120 min. ISO2 4 also increased plasma insulin over the infusion. ISO8 resulted in a 16% decrease in leptin. Saline did not change leptin. SRIH alone decre ased 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 s omatostatin reduce plasma leptin in humans. The effect of isoprotereno l is likely mediated by beta-adrenergic receptors, whereas the effect of somatostatin suggests a novel mechanism for the regulation of lepti n.