|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2010-2-1
|
|
pubmed:abstractText |
Ghrelin is a 28-amino-acid peptide secreted predominantly by X/A-like cells of the gastric fundus. Ghrelin increases pancreatic beta-cell proliferation and survival via sequential activation of phosphatidylinositol-3 kinase (PI3K) and Akt. The transcription regulator Foxo1 is a prominent effector of PI3K/Akt; when it is inhibited, pancreatic beta-cells are protected against fatty-acid-induced apoptosis. We investigated the role of Foxo1 in the protective effect of ghrelin under lipotoxic conditions in the MIN6 pancreatic beta-cell line. Results showed that ghrelin promoted cell proliferation and attenuated palmitate-induced apoptosis in cultured MIN6 cells. Nuclear exclusion of Foxo1 was necessary for the function of ghrelin. Treatment of MIN6 cells with palmitate and ghrelin-induced rapid nuclear exclusion and phosphorylation of Foxo1. Unlike the JNK inhibitor SP600125, Akt inhibitor IV blocked the anti-lipotoxic effect of ghrelin and stimulated Foxo1 nuclear translocation. In addition, treatment with ghrelin combined with SP600125 showed a synergistic antiapoptotic effect in palmitate-treated MIN6 cells. Ghrelin also inhibited the endoplasmic reticulum stress pathway of apoptosis in MIN6 cells, decreased expression of cytoplasmic triglyceride, and downregulated gene expression of Bcl-2-associated X (BAX), sterol-response element-binding protein 1c (SREBP1c), and C/EBP homologous protein (CHOP-10). These findings suggest that ghrelin protects pancreatic beta-cells from lipotoxicity by inhibiting the nuclear translocation of Foxo1.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anthracenes,
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Ddit3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxo1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ghrelin,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Palmitic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Albumin, Bovine,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor CHOP,
http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/anthra(1,9-cd)pyrazol-6(2H)-one,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
1873-5169
|
|
pubmed:author |
|
|
pubmed:copyrightInfo |
(c) 2009 Elsevier Inc. All rights reserved.
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
31
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
307-14
|
|
pubmed:meshHeading |
pubmed-meshheading:19944124-Animals,
pubmed-meshheading:19944124-Anthracenes,
pubmed-meshheading:19944124-Apoptosis,
pubmed-meshheading:19944124-Caspase 3,
pubmed-meshheading:19944124-Cell Line,
pubmed-meshheading:19944124-Cell Nucleus,
pubmed-meshheading:19944124-Cell Proliferation,
pubmed-meshheading:19944124-Cytoplasm,
pubmed-meshheading:19944124-Endoplasmic Reticulum,
pubmed-meshheading:19944124-Forkhead Transcription Factors,
pubmed-meshheading:19944124-Gene Expression,
pubmed-meshheading:19944124-Ghrelin,
pubmed-meshheading:19944124-Insulin-Secreting Cells,
pubmed-meshheading:19944124-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:19944124-Lipid Metabolism,
pubmed-meshheading:19944124-Mice,
pubmed-meshheading:19944124-Palmitic Acid,
pubmed-meshheading:19944124-Phosphorylation,
pubmed-meshheading:19944124-Protein Kinase Inhibitors,
pubmed-meshheading:19944124-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19944124-Serum Albumin, Bovine,
pubmed-meshheading:19944124-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:19944124-Stress, Physiological,
pubmed-meshheading:19944124-Transcription Factor CHOP,
pubmed-meshheading:19944124-Triglycerides,
pubmed-meshheading:19944124-bcl-2-Associated X Protein
|
|
pubmed:year |
2010
|
|
pubmed:articleTitle |
Inhibition of Foxo1 mediates protective effects of ghrelin against lipotoxicity in MIN6 pancreatic beta-cells.
|
|
pubmed:affiliation |
Department of Endocrinology, First Hospital of China Medical University, No. 155, Nanjingbei Street, Heping District, Shenyang 110001, Liaoning, China.
|
|
pubmed:publicationType |
Journal Article
|
