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Acylated and unacyl...
Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-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.
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Granata, Riccarda (författare)
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Settanni, Fabio (författare)
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Biancone, Luigi (författare)
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Trovato, Letizia (författare)
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Nano, Rita (författare)
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Bertuzzi, Federico (författare)
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Destefanis, Silvia (författare)
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Annunziata, Marta (författare)
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Martinetti, Monica (författare)
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Catapano, Filomena (författare)
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Ghè, Corrado (författare)
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- Isgaard, Jörgen, 1959 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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Papotti, Mauro (författare)
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Ghigo, Ezio (författare)
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Muccioli, Giampiero (författare)
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(creator_code:org_t)
- The Endocrine Society, 2007
- 2007
- Engelska.
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:2, s. 512-29
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https://academic.oup...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- 1-Phosphatidylinositol 3-Kinase
- metabolism
- Acylation
- Animals
- Apoptosis
- drug effects
- Binding Sites
- Cell Line
- Cell Proliferation
- drug effects
- Cricetinae
- Culture Media
- Serum-Free
- pharmacology
- Cyclic AMP
- physiology
- Cyclic AMP-Dependent Protein Kinases
- physiology
- Drug Synergism
- Extracellular Signal-Regulated MAP Kinases
- physiology
- GTP-Binding Protein alpha Subunits
- Gs
- metabolism
- Humans
- Insulin
- secretion
- Insulin-Secreting Cells
- cytology
- physiology
- secretion
- Interferon Type II
- pharmacology
- Islets of Langerhans
- cytology
- physiology
- Nitric Oxide
- antagonists & inhibitors
- biosynthesis
- Peptide Hormones
- chemistry
- pharmacology
- Proto-Oncogene Proteins c-akt
- metabolism
- Receptors
- G-Protein-Coupled
- metabolism
- Signal Transduction
- physiology
- Tumor Necrosis Factor-alpha
- pharmacology
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Granata, Riccard ...
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Settanni, Fabio
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Biancone, Luigi
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Trovato, Letizia
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Nano, Rita
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Bertuzzi, Federi ...
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visa fler...
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Destefanis, Silv ...
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Annunziata, Mart ...
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Martinetti, Moni ...
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Catapano, Filome ...
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Ghè, Corrado
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Isgaard, Jörgen, ...
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Papotti, Mauro
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Ghigo, Ezio
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Muccioli, Giampi ...
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visa färre...
- Artiklar i publikationen
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Endocrinology
- Av lärosätet
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Göteborgs universitet