瘦素通过激活磷酸二酯酶3B来抑制胰岛素分泌。
Leptin inhibits insulin secretion by activation of phosphodiesterase 3B.
作者信息
Zhao A Z, Bornfeldt K E, Beavo J A
机构信息
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
出版信息
J Clin Invest. 1998 Sep 1;102(5):869-73. doi: 10.1172/JCI3920.
Abstract
The molecular signaling events by which leptin exerts its functions in vivo are not well delineated. Here, we show a novel leptin signaling mechanism that requires phosphoinositide 3-kinase (PI 3-kinase)-dependent activation of cyclic nucleotide phosphodiesterase 3B (PDE3B) and subsequent suppression of cAMP levels. In pancreatic beta cells, leptin causes the activation of PDE3B, which leads to marked inhibition of glucagon-like peptide-1-stimulated insulin secretion. The effect of leptin is abolished when insulin secretion is induced with cAMP analogues that cannot be hydrolyzed by PDE3B. Selective inhibitors of PDE3B and PI 3-kinase completely prevent the leptin effect on insulin secretion and cAMP accumulation. The results demonstrate that one of the physiological effects of leptin, suppression of insulin secretion, is mediated through activation of PDE3B and suggest PDE3B as a mediator of leptin action in other tissues.
摘要
瘦素在体内发挥功能的分子信号转导事件尚未完全阐明。在此，我们展示了一种新的瘦素信号传导机制，该机制需要磷酸肌醇3激酶（PI 3激酶）依赖性激活环核苷酸磷酸二酯酶3B（PDE3B）并随后抑制cAMP水平。在胰腺β细胞中，瘦素导致PDE3B的激活，这导致胰高血糖素样肽-1刺激的胰岛素分泌受到显著抑制。当用不能被PDE3B水解的cAMP类似物诱导胰岛素分泌时，瘦素的作用被消除。PDE3B和PI 3激酶的选择性抑制剂完全阻止了瘦素对胰岛素分泌和cAMP积累的影响。结果表明，瘦素的一种生理作用，即抑制胰岛素分泌，是通过PDE3B的激活介导的，并提示PDE3B是瘦素在其他组织中作用的介质。
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