Gene therapy of diabetes: glucose-stimulated insulin secretion in a human hepatoma cell line (HEP G2ins/g)

Gene Therapy
A M SimpsonM Camacho

Abstract

In order to design a feasible somatic cell gene delivery system for the treatment of type I diabetes, a suitable cell type needs to be determined. We have previously shown that the stable transfection of the full-length insulin cDNA into the human liver cell line, (HEP G2ins) resulted in synthesis, storage and acute regulated release of insulin to analogues of cAMP, but not to the physiological stimulus glucose. In attempting to explain the lack of glucose responsiveness of the HEP G2ins cells we have stably transfected these cells with the human islet glucose transporter GLUT 2 (HEP, G2ins/g cells). The HEP G2ins/g cell clones exhibit glucose-stimulated insulin secretion and glucose potentiation of the secretory response to nonglucose secretagogues. While glucose responsiveness commenced at a lower concentration than normal islets, a secretion curve approaching normal physiological conditions was generated. Immunoelectron microscopy revealed the presence of insulin-containing granules, similar in size and appearance to those of the normal beta cell. These results demonstrate that while it is most likely that the HEP G2ins/g cell line predominantly secretes insulin via the constitutive pathway, significant acute regulated relea...Continue Reading

Citations

Jan 30, 2002·Trends in Molecular Medicine·Ji-Won Yoon, Hee-Sook Jun
Nov 13, 2008·Cytotechnology·Patrick GammellMartin Clynes
Oct 28, 2003·Human Gene Therapy·Darin E OlsonPeter M Thulé
Sep 6, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Guo Jun LiuDonald K Martin
Jun 25, 2005·BMC Bioinformatics·Per StenbergJan Larsson
Oct 2, 2007·BMC Bioinformatics·Thomas Schlitt, Alvis Brazma
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Oct 9, 2007·Life Sciences·Revati J TatakeRichard D Schneiderman
Jan 8, 2013·The Journal of Gene Medicine·Binhai RenAnn M Simpson
Jun 2, 2015·Molecular Therapy. Methods & Clinical Development·Janet LawandiAnn M Simpson
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