Impact of defined matrix interactions on insulin production by cultured human beta-cells: effect on insulin content, secretion, and gene transcription.
Diabetes
; 55(10): 2723-9, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-17003336
ABSTRACT
The impact of extracellular matrix on insulin production needs to be understood both to optimize the derivation of functional beta-cells for transplantation and to understand mechanisms controlling islet neogenesis and glucose homeostasis. In this study, we present evidence that adhesion to some common matrix constituents has a profound impact on the transcription, secretion, and storage of insulin by human beta-cells. The integrin-dependent adhesion of fetal beta-cells to both collagen IV and vitronectin induces significant glucose-independent insulin secretion and a substantial reciprocal decline in insulin content. Collagen IV, but not vitronectin, induces comparable responses in adult beta-cells. Inhibition of extracellular signal-regulated kinase activation abrogates matrix-induced insulin secretion and effectively preserves the insulin content of adherent beta-cells. Using real-time PCR, we demonstrate that adhesion of both fetal and adult beta-cells to collagen IV and vitronectin also results in the marked suppression of insulin gene transcription. Based on these findings, we contend that integrin-dependent adhesion and signaling in response to certain matrices can have a significant negative impact on insulin production by primary human beta-cells. Such responses were not found to be associated with cell death but may precede beta-cell dedifferentiation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Integrinas
/
Células Secretoras de Insulina
/
Matriz Extracelular
/
Insulina
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article