Insulin drives glucose-dependent insulinotropic peptide expression via glucose-dependent regulation of FoxO1 and LEF1/ß-catenin.
Biochim Biophys Acta
; 1839(11): 1141-50, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-25091498
ABSTRACT
Minutes after ingestion of fat or carbohydrates, vesicles stored in enteroendocrine cells release their content of incretin peptide hormones that, together with absorbed glucose, enhance insulin secretion by beta-pancreatic cells. Freshly-made incretins must therefore be packed into new vesicles in anticipation of the next meal with cells adjusting new incretin production to be proportional to the level of previous insulin release and absorbed blood glucose. Here we show that insulin stimulates the expression of the major human incretin, glucose-dependent insulinotropic peptide (GIP) in enteroendocrine cells but requires glucose to do it. Akt-dependent release of FoxO1 and glucose-dependent binding of LEF1/ß-catenin mediate induction of Gip expression while insulin-induced phosphorylation of ß-catenin does not alter its localization or transcriptional activity in enteroendocrine cells. Our results reveal a glucose-regulated feedback loop at the entero-insular axis, where glucose levels determine basal and insulin-induced Gip expression; GIP stimulation of insulin release, physiologically ensures a fine control of glucose homeostasis. How enteroendocrine cells adjust incretin production to replace incretin stores for future use is a key issue because GIP malfunction is linked to all forms of diabetes.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polipeptídeo Inibidor Gástrico
/
Beta Catenina
/
Fator 1 de Ligação ao Facilitador Linfoide
/
Fatores de Transcrição Forkhead
/
Glucose
/
Insulina
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article