Source:http://linkedlifedata.com/resource/pubmed/id/11272140
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2001-2-22
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| pubmed:abstractText |
Neogenesis is crucial for the maintenance of beta-cell mass in the human pancreas and possibly for the outcome of clinical islet transplantation. To date, no studies have reported a stimulation of human beta-cell neogenesis in vivo. Therefore, we investigated whether human alpha-, beta-, and duct cell growth can be stimulated when human islets are xenotransplanted to obese hyperglycemic-hyperinsulinemic ob/ob mice immunosuppressed with anti-lymphocyte serum. Moreover, we wanted to study whether beta-cell growth and duct-to-beta-cell differentiation were induced in the hepatocyte growth factor (HGF)-dependent compensatory kidney growth model. For that purpose, we evaluated human islets grafted to nude (nu/nu) mice before uninephrectomy of the contralateral kidney for DNA-synthesis and duct cell expression of the beta-cell-specific transcription factor Nkx 6.1 as an estimate of differentiation. Human islet grafts were well preserved after 2 weeks when transplanted to ob/ob mice during anti-lymphocyte immunosuppression. Both human beta-cells (P < 0.01) and duct cells (P < 0.001) were growth stimulated when islets were transplanted to ob/ob mice. We also observed a correlation between increased duct cell proliferation and increased organ donor age (P = 0.02). Moreover, duct (P < 0.05) and beta-cell (P < 0.05) proliferation, as well as duct cell Nkx 6.1 expression (P < 0.05), were enhanced by the compensatory kidney growth after uninephrectomy. We conclude that it is possible to stimulate human beta-cell neogenesis in vivo, provided that the recipient carries certain growth-stimulatory traits. Furthermore, it seems that duct cell proliferation increases with increasing organ donor age. Altogether, these data and previous results from our laboratory suggest that human beta-cell neogenesis becomes more dependent on differentiation and less dependent on proliferation with increasing age.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0012-1797
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
50
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
301-7
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11272140-Adaptation, Physiological,
pubmed-meshheading:11272140-Adolescent,
pubmed-meshheading:11272140-Adult,
pubmed-meshheading:11272140-Animals,
pubmed-meshheading:11272140-Cell Differentiation,
pubmed-meshheading:11272140-Cell Division,
pubmed-meshheading:11272140-Child,
pubmed-meshheading:11272140-Female,
pubmed-meshheading:11272140-Humans,
pubmed-meshheading:11272140-Immunosuppression,
pubmed-meshheading:11272140-Islets of Langerhans,
pubmed-meshheading:11272140-Islets of Langerhans Transplantation,
pubmed-meshheading:11272140-Leptin,
pubmed-meshheading:11272140-Male,
pubmed-meshheading:11272140-Mice,
pubmed-meshheading:11272140-Mice, Inbred C57BL,
pubmed-meshheading:11272140-Middle Aged,
pubmed-meshheading:11272140-Nephrectomy,
pubmed-meshheading:11272140-Swine,
pubmed-meshheading:11272140-Transplantation, Heterologous
|
| pubmed:year |
2001
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| pubmed:articleTitle |
Stimulated endocrine cell proliferation and differentiation in transplanted human pancreatic islets: effects of the ob gene and compensatory growth of the implantation organ.
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| pubmed:affiliation |
Department of Medical Cell Biology, Uppsala University, Sweden. btyrberg@ucsd.edu
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|