The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
Epac: A New cAMP-Binding Protein in Support of Glucagon-Like Peptide-1 Receptor-Mediated Signal Transduction in the Pancreatic β-Cell
Open accessAbstract
Recently published studies of islet cell function reveal unexpected features of glucagon-like peptide-1 (GLP-1) receptor-mediated signal transduction in the pancreatic β-cell. Although GLP-1 is established to be a cAMP-elevating agent, these studies demonstrate that protein kinase A (PKA) is not the only cAMP-binding protein by which GLP-1 acts. Instead, an alternative cAMP signaling mechanism has been described, one in which GLP-1 activates cAMP-binding proteins designated as cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs, also known as Epac). Two variants of Epac (Epac1 and Epac2) are expressed in β-cells, and downregulation of Epac function diminishes stimulatory effects of GLP-1 on β-cell Ca2+ signaling and insulin secretion. Of particular note are new reports demonstrating that Epac couples β-cell cAMP production to the stimulation of fast Ca2+-dependent exocytosis. It is also reported that Epac mediates the cAMP-dependent mobilization of Ca2+ from intracellular Ca2+ stores. This is a process of Ca2+-induced Ca2+ release (CICR), and it generates an increase of [Ca2+]i that may serve as a direct stimulus for mitochondrial ATP production and secretory granule exocytosis. This article summarizes new findings concerning GLP-1 receptor-mediated signal transduction and seeks to define the relative importance of Epac and PKA to β-cell stimulus-secretion coupling.
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Cites
Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
de Rooij, J., Zwartkruis, F. J. T., Verheijen, M. H. G., Cool, R. H., Nijman, S. M. B., Wittinghofer, A., & Bos, J. L. (1998) · Nature · doi:10.1038/24884 · Cited by 1,969
A Family of cAMP-Binding Proteins That Directly Activate Rap1
Kawasaki, H., Springett, G. M., Mochizuki, N., Toki, S., Nakaya, M., Matsuda, M., Housman, D. E., & Graybiel, A. M. (1998) · Science · doi:10.1126/science.282.5397.2275 · Cited by 1,362
Triggering and amplifying pathways of regulation of insulin secretion by glucose.
Henquin, J. C. (2000) · Diabetes · doi:10.2337/diabetes.49.11.1751 · Cited by 1,201
Kieffer, T. J., & Francis Habener, J. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.6.0385 · Cited by 1,062
Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation
Stork, P. J. S., & Schmitt, J. M. (2002) · Trends in Cell Biology · doi:10.1016/s0962-8924(02)02294-8 · Cited by 897
Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion
Prentki, M., & Matschinsky, F. M. (1987) · Physiological Reviews · doi:10.1152/physrev.1987.67.4.1185 · Cited by 774
Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion
Wang, Y., Okamoto, M., Schmitz, F., Hofmann, K., & Südhof, T. C. (1997) · Nature · doi:10.1038/41580 · Cited by 684
A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
Enserink, J. M., Christensen, A. E., de Rooij, J., van Triest, M., Schwede, F., Genieser, H. G., Døskeland, S. O., Blank, J. L., & Bos, J. L. (2002) · Nature Cell Biology · doi:10.1038/ncb874 · Cited by 625
Drucker, D. J. (1998) · Diabetes · doi:10.2337/diab.47.2.159 · Cited by 601
Holz IV, G. G., Kiihtreiber, W. M., & Habener, J. F. (1993) · Nature · doi:10.1038/361362a0 · Cited by 594
Research works printed but not linked: 2
- Lindstrom P, Norlund L, Sehlin J, Taljedal IB: Effects of 5-hydroxytryptamine on rubidium ion fluxes and insulin release in cultured pancreatic islets. Endocrinology 115: 2121–2125,1984 · doi:10.1210/endo-115-5-2021
- Harris TE, Persaud SJ, Jones PM: Pseudosubstrate inhibition of cyclic AMP-dependent protein kinase in intact pancreatic islets: effects on cyclic AMP-dependent and glucose-dependent insulin secretion. Biochem Biophys Res Commun 232: 648–651,1997 · doi:10.1006/bbrc.1997.6344
Cited by
The Physiology of Glucagon-like Peptide 1
Holst, J. J. (2007) · Physiological Reviews · doi:10.1152/physrev.00034.2006 · Cited by 3,371
The biology of incretin hormones
Drucker, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.004 · Cited by 2,210
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
Fluorescent Proteins and Their Applications in Imaging Living Cells and Tissues
Chudakov, D. M., Matz, M. V., Lukyanov, S., & Lukyanov, K. A. (2010) · Physiological Reviews · doi:10.1152/physrev.00038.2009 · Cited by 1,375
Glucagon-like peptide-1 receptor: mechanisms and advances in therapy
Zheng, Z., Zong, Y., Ma, Y., Tian, Y., Pang, Y., Zhang, C., & Gao, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01931-z · Cited by 1,036
Metadata
- Authors
- Holz, G. G.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-01-01
- Volume
- 53
- Issue
- 1
- Pages
- 5-13
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2145824107
- Cited by
- 391
- References
- 78
- FWCI
- 21.81
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Holz, G. G. (2004). Epac: A New cAMP-Binding Protein in Support of Glucagon-Like Peptide-1 Receptor-Mediated Signal Transduction in the Pancreatic β-Cell. Diabetes. https://doi.org/10.2337/diabetes.53.1.5
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