Insulin and heregulin-beta1 upregulate guanylyl cyclase C expression in rat hepatocytes: reversal by phosphodiesterase-3 inhibition.
Insulin and heregulin-beta1 upregulate guanylyl cyclase C expression in rat hepatocytes: reversal by phosphodiesterase-3 inhibition.
复制标题
胰岛素和调蛋白-β1 上调大鼠肝细胞中鸟苷酸环化酶 C 的表达：通过磷酸二酯酶 3 抑制逆转。
DOI：
10.1016/s0898-6568(01)00179-6
复制
发表时间：
2001
影响因子：
4.8
通讯作者：
Russell,WE
中科院分区：
文献类型：
--
作者：
Scheving,LA;Russell,WE
鸟苷酸环化酶C（GC-C）是鸟苷素和尿鸟苷素激素的受体。虽然主要在大鼠肠道中表达，但GC-C在新生儿或再生生长期间或在急性期反应期间也在肝脏中表达。对GC-C表达的肝脏调节知之甚少。通过免疫印迹分析在无血清培养基中生长的原代大鼠肝细胞蛋白质，评价各种肝生长或急性期调节剂对GC-C表达的影响。胰岛素和heregulin-β1在细胞培养24 h后强烈刺激GC-C表达。几种不同的激素和试剂抑制这种作用，包括转化生长因子β（TGF-β），以及磷脂酰肌醇3-激酶（PI-3-激酶）和磷酸二酯酶3（PDE-3，胰岛素和PI-3-激酶依赖性酶）的抑制剂。PDE-3对cAMP水平的隔室下调可能是在GC-C合成中达到高潮的激素作用中的关键步骤。
Guanylyl cyclase C (GC-C) is the receptor for the hormones guanylin and uroguanylin. Although primarily expressed in the rat intestine, GC-C is also expressed in the liver during neonatal or regenerative growth or during the acute phase response. Little is known about the hepatic regulation of GC-C expression. The influence of various hepatic growth or acute phase regulators on GC-C expression was evaluated by immunoblot analysis of protein from primary rat hepatocytes grown in a serum-free medium. Insulin and heregulin-β1 strongly stimulated GC-C expression by 24 h of cell culture. Several different hormones and agents suppressed this action, including transforming growth factor β (TGF-β), as well as inhibitors of phosphatidylinositol 3-kinase (PI-3-kinase) and phosphodiesterase 3 (PDE-3, an insulin- and PI-3-kinase-dependent enzyme). The compartmental downregulation of cAMP levels by PDE-3 may be a critical step in the hormonal action that culminates in GC-C synthesis.