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dc.contributor.author
Aggarwal, Gaurav
dc.contributor.author
Ramachandran, Vijaya
dc.contributor.author
Javeed, Naureen
dc.contributor.author
Arumugam, Thiruvengadam
dc.contributor.author
Dutta, Shamit
dc.contributor.author
Klee, George G.
dc.contributor.author
Klee, Eric W.
dc.contributor.author
Smyrk, Thomas C.
dc.contributor.author
Bamlet, William
dc.contributor.author
Han, Jing Jing
dc.contributor.author
Rumie Vittar, Natalia Belen
dc.contributor.author
De Andrade, Mariza
dc.contributor.author
Mukhopadhyay, Debabrata
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Petersen, Gloria M.
dc.contributor.author
Fernandez Zapico, Martin Ernesto
dc.contributor.author
Logsdon, Craig D.
dc.contributor.author
Chari, Suresh T.
dc.date.available
2023-05-31T18:02:26Z
dc.date.issued
2012-12
dc.identifier.citation
Aggarwal, Gaurav; Ramachandran, Vijaya; Javeed, Naureen; Arumugam, Thiruvengadam; Dutta, Shamit; et al.; Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice; W B Saunders Co-Elsevier Inc; Gastroenterology; 143; 6; 12-2012; 1510-1517
dc.identifier.issn
0016-5085
dc.identifier.uri
http://hdl.handle.net/11336/199199
dc.description.abstract
New-onset diabetes in patients with pancreatic cancer is likely to be a paraneoplastic phenomenon caused by tumor-secreted products. We aimed to identify the diabetogenic secretory product(s) of pancreatic cancer. Methods: Using microarray analysis, we identified adrenomedullin as a potential mediator of diabetes in patients with pancreatic cancer. Adrenomedullin was up-regulated in pancreatic cancer cell lines, in which supernatants reduced insulin signaling in beta cell lines. We performed quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry on human pancreatic cancer and healthy pancreatic tissues (controls) to determine expression of adrenomedullin messenger RNA and protein, respectively. We studied the effects of adrenomedullin on insulin secretion by beta cell lines and whole islets from mice and on glucose tolerance in pancreatic xenografts in mice. We measured plasma levels of adrenomedullin in patients with pancreatic cancer, patients with type 2 diabetes mellitus, and individuals with normal fasting glucose levels (controls). Results: Levels of adrenomedullin messenger RNA and protein were increased in human pancreatic cancer samples compared with controls. Adrenomedullin and conditioned media from pancreatic cell lines inhibited glucose-stimulated insulin secretion from beta cell lines and islets isolated from mice; the effects of conditioned media from pancreatic cancer cells were reduced by small hairpin RNA-mediated knockdown of adrenomedullin. Conversely, overexpression of adrenomedullin in mice with pancreatic cancer led to glucose intolerance. Mean plasma levels of adrenomedullin (femtomoles per liter) were higher in patients with pancreatic cancer compared with patients with diabetes or controls. Levels of adrenomedullin were higher in patients with pancreatic cancer who developed diabetes compared those who did not. Conclusions: Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
W B Saunders Co-Elsevier Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
MECHANISMS
dc.subject
MOUSE MODEL
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PANCREAS
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TUMOR
dc.subject.classification
Otras Ciencias de la Salud
dc.subject.classification
Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-05-29T12:39:01Z
dc.identifier.eissn
1528-0012
dc.journal.volume
143
dc.journal.number
6
dc.journal.pagination
1510-1517
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Philadelphia
dc.description.fil
Fil: Aggarwal, Gaurav. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Ramachandran, Vijaya. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados Unidos
dc.description.fil
Fil: Javeed, Naureen. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Arumugam, Thiruvengadam. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados Unidos
dc.description.fil
Fil: Dutta, Shamit. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Klee, George G.. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Klee, Eric W.. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Smyrk, Thomas C.. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Bamlet, William. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Han, Jing Jing. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Rumie Vittar, Natalia Belen. Mayo Clinic College of Medicine; Estados Unidos. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Biología Molecular. Sección Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: De Andrade, Mariza. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Mukhopadhyay, Debabrata. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Petersen, Gloria M.. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Fernandez Zapico, Martin Ernesto. Mayo Clinic College of Medicine; Estados Unidos
dc.description.fil
Fil: Logsdon, Craig D.. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados Unidos
dc.description.fil
Fil: Chari, Suresh T.. Mayo Clinic College of Medicine; Estados Unidos
dc.journal.title
Gastroenterology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pubmed/22960655
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1053/j.gastro.2012.08.044
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