The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.
Acylated and Unacylated Ghrelin Promote Proliferation and Inhibit Apoptosis of Pancreatic β-Cells and Human Islets: Involvement of 3′,5′-Cyclic Adenosine Monophosphate/Protein Kinase A, Extracellular Signal-Regulated Kinase 1/2, and Phosphatidyl Inositol 3-Kinase/Akt Signaling
Open accessAbstract
Among its pleiotropic actions, ghrelin modulates insulin secretion and glucose metabolism. Herein we investigated the role of ghrelin in pancreatic beta-cell proliferation and apoptosis induced by serum starvation or interferon (IFN)-gamma/TNF-alpha, whose synergism is a major cause for beta-cell destruction in type I diabetes. HIT-T15 beta-cells expressed ghrelin but not ghrelin receptor (GRLN-R), which binds acylated ghrelin (AG) only. However, both unacylated ghrelin (UAG) and AG recognized common high-affinity binding sites on these cells. Either AG or UAG stimulated cell proliferation through Galpha(s) protein and prevented serum starvation- and IFN-gamma/TNF-alpha-induced apoptosis. Antighrelin antibody enhanced apoptosis in either the presence or absence of serum but not cytokines. AG and UAG even up-regulated intracellular cAMP. Blockade of adenylyl cyclase/cAMP/protein kinase A signaling prevented the ghrelin cytoprotective effect. AG and UAG also activated phosphatidyl inositol 3-kinase (PI3K)/Akt and ERK1/2, whereas PI3K and MAPK inhibitors counteracted the ghrelin antiapoptotic effect. Furthermore, AG and UAG stimulated insulin secretion from HIT-T15 cells. In INS-1E beta-cells, which express GRLN-R, AG and UAG caused proliferation and protection against apoptosis through identical signaling pathways. Noteworthy, both peptides inhibited cytokine-induced NO increase in either HIT-T15 or INS-1E cells. Finally, they induced cell survival and protection against apoptosis in human islets of Langerhans. These expressed GRLN-R but showed also UAG and AG binding sites. Our data demonstrate that AG and UAG promote survival of both beta-cells and human islets. These effects are independent of GRLN-R, are likely mediated by AG/UAG binding sites, and involve cAMP/PKA, ERK1/2, and PI3K/Akt.
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Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids
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Ghrelin induces adiposity in rodents
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Ghrelin regulation of glucose metabolism
Poher, A.-L., Tschöp, M. H., & Müller, T. D. (2018) · Peptides · doi:10.1016/j.peptides.2017.12.015 · Cited by 186
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Metadata
- Authors
- Granata, R., Settanni, F., Biancone, L., Trovato, L., Nano, R., Bertuzzi, F., Destefanis, S., Annunziata, M., Martinetti, M., Catapano, F., Ghè, C., Isgaard, J., Papotti, M., Ghigo, E., & Muccioli, G.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2007-02
- Volume
- 148
- Issue
- 2
- Pages
- 512-529
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2073118840
- Cited by
- 294
- References
- 84
- FWCI
- 19.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Granata, R., Settanni, F., Biancone, L., Trovato, L., Nano, R., Bertuzzi, F., Destefanis, S., Annunziata, M., Martinetti, M., Catapano, F., Ghè, C., Isgaard, J., Papotti, M., Ghigo, E., & Muccioli, G. (2007). Acylated and Unacylated Ghrelin Promote Proliferation and Inhibit Apoptosis of Pancreatic β-Cells and Human Islets: Involvement of 3′,5′-Cyclic Adenosine Monophosphate/Protein Kinase A, Extracellular Signal-Regulated Kinase 1/2, and Phosphatidyl Inositol 3-Kinase/Akt Signaling. Endocrinology. https://doi.org/10.1210/en.2006-0266
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