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Glucose-regulated insulin production from genetically engineered human non-beta cells.
Tatake, Revati J; O'Neill, Margaret M; Kennedy, Charles A; Reale, Virginia D; Runyan, Jacob D; Monaco, Kelli-Ann D; Yu, Kyung; Osborne, William R; Barton, Randall W; Schneiderman, Richard D.
Afiliação
  • Tatake RJ; Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA. rtatake@rdg.boehringer-ingelheim.com
Life Sci ; 81(17-18): 1346-54, 2007 Oct 13.
Article em En | MEDLINE | ID: mdl-17920636
ABSTRACT
In this report we describe development and characterization of four human cell lines that are able to secrete insulin and C-peptide in response to higher concentrations of glucose. These cell lines have been developed by stably and constitutively expressing human proinsulin with a furin-cleavable site, whereas expression of furin is regulated by glucose concentration. These cell lines have been cloned and, therefore, the transgene in each cell is located in an identical location of the genome leading to a uniform expression. Cloning has also allowed us to identify cell lines with more desirable properties such as higher basal insulin secretion and/or better glucose responsiveness. We have further shown that the insulin produced by these cells is biologically active and induces normoglycemia when injected in diabetic animals. Our objective in initiating these studies was to identify a cell line that could serve as a surrogate beta cell line for therapeutic intervention in type I diabetic patients.
Assuntos
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Base de dados: MEDLINE Assunto principal: Engenharia Genética / Glucose / Insulina Limite: Animals / Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Engenharia Genética / Glucose / Insulina Limite: Animals / Humans Idioma: En Ano de publicação: 2007 Tipo de documento: Article