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Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene

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dc.contributor.author Encina, Gonzalo
dc.contributor.author Ezquer, Fernando
dc.contributor.author Conget, Paulette
dc.contributor.author Israel, Yedy
dc.date.accessioned 2016-12-16T19:56:27Z
dc.date.available 2016-12-16T19:56:27Z
dc.date.issued 2011
dc.identifier.citation Biological Research, 2011, vol. 44, n° 3, p. 301-305
dc.identifier.uri http://hdl.handle.net/11447/901
dc.description.abstract Transgenic mice carrying the human insulin gene driven by the K-cell glucose-dependent insulinotropic peptide (GIP) promoter secrete insulin and display normal glucose tolerance tests after their pancreatic beta-cells have been destroyed. Establishing the existence of other types of cells that can process and secrete transgenic insulin would help the development of new gene therapy strategies to treat patients with diabetes mellitus. It is noted that in addition to GIP secreting K-cells, the glucagon-like peptide 1 (GLP-1) generating L-cells share/many similarities to pancreatic p-cells, including the peptidases required for proinsulin processing, hormone storage and a glucose-stimulated hormone secretion mechanism. In the present study, we demonstrate that not only K-cells, but also L-cells engineered with the human preproinsulin gene are able to synthesize, store and, upon glucose stimulation, release mature insulin. When the mouse enteroendocrine STC-1 cell line was transfected with the human preproinsulin gene, driven either by the K-cell specific GIP promoter or by the constitutive cytomegalovirus (CMV) promoter, human insulin co-localizes in vesicles that contain GIP (GIP or CMV promoter) or GLP-1 (CMV promoter). Exposure to glucose of engineered STC-1 cells led to a marked insulin secretion, which was 7-fold greater when the insulin gene was driven by the CMV promoter (expressed both in K-cells and L-cells) than when it was driven by the GIP promoter (expressed only in K-cells). Thus, besides pancreatic beta-cells, both gastrointestinal enteroendocrine K-cells and L-cells can be selected as the target cell in a gene therapy strategy to treat patients with type 1 diabetes mellitus.
dc.language.iso en_US
dc.subject Type 1 diabetes mellitus
dc.subject Preproinsulin gene
dc.subject Gastrointestinal enteroendocrine cells
dc.subject K-cells
dc.subject L-cells
dc.title Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene
dc.type Artículo


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