Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rail primary adipocytes
Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rail primary adipocytes
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DOI：
10.1042/bj20061478
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发表时间：
2007-05-01
影响因子：
4.1
通讯作者：
Zhao, Allan Z.
中科院分区：
文献类型：
--
作者：
Cong, Li;Chen, Ke;Zhao, Allan Z.
脂联素密切参与胰岛素敏感性、碳水化合物和脂质代谢以及心血管功能的调节。肥胖和 2 型糖尿病患者的脂联素循环浓度降低。本研究试图阐明大鼠原代脂肪细胞脂联素分泌和表达调节的机制。 β-激动剂异丙肾上腺素以剂量依赖性方式降低原代脂肪细胞中脂联素的分泌和表达。重要的是，这种抑制作用可以被胰岛素阻断。异丙肾上腺素和胰岛素的相反作用可以通过细胞内 cAMP 水平的差异调节来解释，因为 cAMP 类似物以类似于异丙肾上腺素的方式抑制脂联素分泌和表达，而胰岛素则阻断可被 PDE（磷酸二酯酶）水解的 cAMP 类似物的抑制作用。一种特定的 PDE3 抑制剂米力农和 PI3K（磷酸肌醇 3-激酶）抑制剂消除了胰岛素对脂联素分泌和表达的影响。在同一研究中，瘦素的分泌和表达显示出与脂联素相似的调节模式。我们得出的结论是，胰岛素和β-激动剂以相反的方式直接作用于脂肪细胞，调节脂联素和瘦素的产生，并且PI3K-PDE3B-cAMP途径介导胰岛素的作用，以恢复β-激动剂/cAMP抑制的这两种脂肪因子的分泌和表达。
Adiponectin is intimately involved in the regulation of insulin sensitivity, carbohydrate and lipid metabolism, and cardiovascular functions. The circulating concentration of adiponectin is decreased in obesity and Type 2 diabetes. The present study attempts to elucidate the mechanisms underlying the regulation of adiponectin secretion and expression in rat primary adipocytes. The beta-agonist, isoprenaline, decreased adiponectin secretion and expression in a dose-dependent manner in primary adipocytes. Importantly, such an inhibitory effect could be blocked by insulin. The opposing effects of isoprenaline and insulin could be explained by differential regulation of intracellular cAMP levels, since cAMP analogues suppressed adiponectin secretion and expression in a fashion similar to isoprenaline, and insulin blocked the inhibitory effects of the cAMP analogue hydrolysable by PDE (phosphodiesterase). A specific PDE3 inhibitor, milrinone, and PI3K (phosphoinositide 3-kinase) inhibitors abolished the effects of insulin on adiponectin secretion and expression. In the same studies, leptin secretion and expression displayed a similar pattern of regulation to adiponectin. We conclude that insulin and beta-agonists act directly at the adipocytes in opposing fashions to regulate the production of adiponectin and leptin, and that a PI3K-PDE3B-cAMP pathway mediates the effects of insulin to restore beta-agonist/cAMP-suppressed secretion and expression of these two adipokines.