Artículo
Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion
Flores, Luis Emilio
; del Zotto, Hector Herminio
; Fragapane, Florencia; Maiztegui, Barbara
; Román, Carolina Lisi
; Boschero, Antonio C.; Gagliardino, Juan Jose
Fecha de publicación:
08/2014
Editorial:
Elsevier Science
Revista:
Regulatory Peptides
ISSN:
0167-0115
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a “physiological” positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.
Palabras clave:
Ingap
,
Insulin Secretion
,
Sirna
,
Hamsters
,
Isolated Islets
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Articulos(CENEXA)
Articulos de CENTRO DE ENDOCRINOLOGIA EXP.Y APLICADA (I)
Articulos de CENTRO DE ENDOCRINOLOGIA EXP.Y APLICADA (I)
Citación
Flores, Luis Emilio; del Zotto, Hector Herminio; Fragapane, Florencia; Maiztegui, Barbara; Román, Carolina Lisi; et al.; Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion; Elsevier Science; Regulatory Peptides; 192-193; 8-2014; 30-34
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