Title:
Insulin secretion dynamics of recombinant hepatic and intestinal cells

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dc.contributor.advisor Sambanis, Athanassios
dc.contributor.author Gulino, Angela Marie en_US
dc.contributor.committeeMember Boyan, Barbara D.
dc.contributor.committeeMember Peter Thule
dc.contributor.department Biomedical Engineering en_US
dc.date.accessioned 2009-06-08T19:29:31Z
dc.date.available 2009-06-08T19:29:31Z
dc.date.issued 2008-03-31 en_US
dc.description.abstract Hepatic and intestinal endocrine cells are potentially helpful targets for recombinant insulin expression. As the two cell types exhibit different secretion kinetics,it has been hypothesized that a combination of the two would better approximate insulin secretion kinetics from normal, functioning beta-cells than either cell type alone. This hypothesis was tested using two hepatic cell lines transiently transduced with one of three adenoviruses for insulin expression along with a stably transfected recombinant intestinal L cell line. The insulin secretion kinetics were analyzed for both the hepatic and intestinal cells to determine the potential of combining them to reproduce the insulin secretion kinetics of a normal, functioning beta-cell. It was observed that the two recombinant hepatic cell lines secreted insulin in a more sustained manner exhibiting slower release kinetics. They also exhibited an increase in insulin secretion when stimulated by the cocktail of nutrient secretagogues (glucose and meat hydrolysate) versus stimulating with only glucose. The cells transduced with the adenovirus containing an additional cytomegalovirus (CMV) promoter and green fluorescent protein (GFP) exhibited the highest insulin secretion after stimulation, whereas the cells transduced with an adenovirus encoding for destabilized preproinsulin mRNA exhibited the lowest secretion rates. The recombinant intestinal cell line (GLUTag-INS) secreted insulin with rapid kinetics upon stimulation, apparently due to the presence of secretory granules containing pre-synthesized insulin. The experiments demonstrated that the cells stimulated with medium containing only meat hydrolysate exhibited a significantly higher insulin secretion relative to secretagogue-free controls. The insulin secretion was not further enhanced when meat hydrolysate was combined with glucose. en_US
dc.description.degree M.S. en_US
dc.identifier.uri http://hdl.handle.net/1853/28220
dc.publisher Georgia Institute of Technology en_US
dc.subject Genetic engineering en_US
dc.subject Diabetes en_US
dc.subject Liver en_US
dc.subject Insulin en_US
dc.subject Kinetics en_US
dc.subject Intestinal en_US
dc.subject.lcsh Liver cells
dc.subject.lcsh Intestines
dc.subject.lcsh Endocrinology
dc.subject.lcsh Recombinant human insulin
dc.subject.lcsh Pancreatic beta cells
dc.title Insulin secretion dynamics of recombinant hepatic and intestinal cells en_US
dc.type Text
dc.type.genre Thesis
dspace.entity.type Publication
local.contributor.advisor Sambanis, Athanassios
local.contributor.corporatename Wallace H. Coulter Department of Biomedical Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication 90a12241-15c3-4cbf-bc27-724c028b8fc1
relation.isOrgUnitOfPublication da59be3c-3d0a-41da-91b9-ebe2ecc83b66
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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