葡萄糖和胰高血糖素样肽-1（GLP-1）通过INS-1E胰岛素瘤细胞中不同的腺苷酸环化酶刺激环磷酸腺苷（cAMP）的产生。
Glucose and GLP-1 stimulate cAMP production via distinct adenylyl cyclases in INS-1E insulinoma cells.
作者信息
Ramos Lavoisier S, Zippin Jonathan Hale, Kamenetsky Margarita, Buck Jochen, Levin Lonny R
机构信息
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10065, USA.
出版信息
J Gen Physiol. 2008 Sep;132(3):329-38. doi: 10.1085/jgp.200810044. Epub 2008 Aug 11.
Abstract
In beta cells, both glucose and hormones, such as GLP-1, stimulate production of the second messenger cAMP, but glucose and GLP-1 elicit distinct cellular responses. We now show in INS-1E insulinoma cells that glucose and GLP-1 produce cAMP with distinct kinetics via different adenylyl cyclases. GLP-1 induces a rapid cAMP signal mediated by G protein-responsive transmembrane adenylyl cyclases (tmAC). In contrast, glucose elicits a delayed cAMP rise mediated by bicarbonate, calcium, and ATP-sensitive soluble adenylyl cyclase (sAC). This glucose-induced, sAC-dependent cAMP rise is dependent upon calcium influx and is responsible for the glucose-induced activation of the mitogen-activated protein kinase (ERK1/2) pathway. These results demonstrate that sAC-generated and tmAC-generated cAMP define distinct signaling cascades.
摘要
在β细胞中，葡萄糖和激素（如胰高血糖素样肽-1，GLP-1）均可刺激第二信使环磷酸腺苷（cAMP）的产生，但葡萄糖和GLP-1会引发不同的细胞反应。我们现在在INS-1E胰岛素瘤细胞中发现，葡萄糖和GLP-1通过不同的腺苷酸环化酶产生具有不同动力学的cAMP。GLP-1诱导由G蛋白反应性跨膜腺苷酸环化酶（tmAC）介导的快速cAMP信号。相比之下，葡萄糖引发由碳酸氢盐、钙和ATP敏感的可溶性腺苷酸环化酶（sAC）介导的延迟cAMP升高。这种葡萄糖诱导的、依赖sAC的cAMP升高依赖于钙内流，并负责葡萄糖诱导的丝裂原活化蛋白激酶（ERK1/2）途径的激活。这些结果表明，由sAC产生的cAMP和由tmAC产生的cAMP定义了不同的信号级联反应。
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