Leech C A, Holz G G, Chepurny O, Habener J F
Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Biochem Biophys Res Commun. 2000 Nov 11;278(1):44-7. doi: 10.1006/bbrc.2000.3763.
The insulinotropic hormone glucagon-like peptide-1 (GLP-1) binds to a Gs-coupled receptor on pancreatic beta-cells and potentiates glucose-induced insulin secretion, insulin gene transcription, and beta-cell growth. These stimulatory effects have been attributed to the elevation of intracellular cAMP levels, though it is now apparent that some stimulatory effects of GLP-1 occur independently of the cAMP-mediated activation of protein kinase A (PKA). The nature of this alternative, PKA-independent signaling pathway remains unknown. Here we present evidence for the expression of type 1 and type 2 cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs) in beta-cells. GEFs are activated by their binding of cAMP. Because cAMP-GEFs activate Ras/MAPK proliferation signaling pathways, they may play an important role in PKA-independent, GLP-1-mediated, signaling pathways in the regulation of beta-cell growth and differentiation.
促胰岛素激素胰高血糖素样肽-1（GLP-1）与胰腺β细胞上的Gs偶联受体结合，增强葡萄糖诱导的胰岛素分泌、胰岛素基因转录和β细胞生长。这些刺激作用归因于细胞内cAMP水平的升高，尽管现在很明显GLP-1的一些刺激作用独立于cAMP介导的蛋白激酶A（PKA）激活而发生。这种替代性的、不依赖PKA的信号通路的性质仍然未知。在这里，我们提供了β细胞中1型和2型cAMP调节鸟嘌呤核苷酸交换因子（cAMP-GEFs）表达的证据。GEFs通过与cAMP结合而被激活。由于cAMP-GEFs激活Ras/MAPK增殖信号通路，它们可能在不依赖PKA的、GLP-1介导的信号通路中，在β细胞生长和分化的调节中发挥重要作用。
