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

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 p-cells have been destroyed. Establishing the existence of other types of cells that can proc...

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Autores principales:	Encina,Gonzalo, Ezquer,Fernando, Conget,Paulette, Israel,Yedy
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2011
Materias:	Type 1 diabetes mellitus preproinsulin gene gastrointestinal enteroendocrine cells K-cells L-cells
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000300012
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spelling	oai:scielo:S0716-976020110003000122011-11-07Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin geneEncina,GonzaloEzquer,FernandoConget,PauletteIsrael,Yedy Type 1 diabetes mellitus preproinsulin gene gastrointestinal enteroendocrine cells K-cells L-cells 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 p-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 p-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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.44 n.3 20112011-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000300012en10.4067/S0716-97602011000300012
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Type 1 diabetes mellitus preproinsulin gene gastrointestinal enteroendocrine cells K-cells L-cells
spellingShingle	Type 1 diabetes mellitus preproinsulin gene gastrointestinal enteroendocrine cells K-cells L-cells Encina,Gonzalo Ezquer,Fernando Conget,Paulette Israel,Yedy Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene
description	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 p-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 p-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.
author	Encina,Gonzalo Ezquer,Fernando Conget,Paulette Israel,Yedy
author_facet	Encina,Gonzalo Ezquer,Fernando Conget,Paulette Israel,Yedy
author_sort	Encina,Gonzalo
title	Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene
title_short	Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene
title_full	Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene
title_fullStr	Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene
title_full_unstemmed	Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene
title_sort	insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine k-cells and l-cells engineered with the preproinsulin gene
publisher	Sociedad de Biología de Chile
publishDate	2011
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602011000300012
work_keys_str_mv	AT encinagonzalo insulinissecreteduponglucosestimulationbybothgastrointestinalenteroendocrinekcellsandlcellsengineeredwiththepreproinsulingene AT ezquerfernando insulinissecreteduponglucosestimulationbybothgastrointestinalenteroendocrinekcellsandlcellsengineeredwiththepreproinsulingene AT congetpaulette insulinissecreteduponglucosestimulationbybothgastrointestinalenteroendocrinekcellsandlcellsengineeredwiththepreproinsulingene AT israelyedy insulinissecreteduponglucosestimulationbybothgastrointestinalenteroendocrinekcellsandlcellsengineeredwiththepreproinsulingene
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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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