Document Detail


Glucose-regulated insulin production from genetically engineered human non-beta cells.
MedLine Citation:
PMID:  17920636     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Revati J Tatake; Margaret M O'Neill; Charles A Kennedy; Virginia D Reale; Jacob D Runyan; Kelli-Ann D Monaco; Kyung Yu; William R Osborne; Randall W Barton; Richard D Schneiderman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-09
Journal Detail:
Title:  Life sciences     Volume:  81     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-26     Completed Date:  2007-12-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1346-54     Citation Subset:  IM    
Affiliation:
Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA. rtatake@rdg.boehringer-ingelheim.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose / analysis
C-Peptide / metabolism
Cell Line
Culture Media
DNA, Complementary / genetics
Diabetes Mellitus, Experimental / drug therapy,  metabolism
Genetic Engineering*
Genetic Vectors
Glucose / metabolism*,  pharmacology
Humans
Insulin / secretion*,  therapeutic use*
Islets of Langerhans
Phosphorylation
Phosphotransferases (Alcohol Group Acceptor) / genetics
Plasmids
Proinsulin / genetics
Promoter Regions, Genetic
Rats
Rats, Nude
Receptor, Insulin / metabolism
Retroviridae / genetics
Transfection
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/C-Peptide; 0/Culture Media; 0/DNA, Complementary; 11061-68-0/Insulin; 50-99-7/Glucose; 9035-68-1/Proinsulin; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/phosphoglycerol kinase; EC 2.7.10.1/Receptor, Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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