ErbB3 is required for hyperaminoacidemia-induced pancreatic α cell hyperplasia.
J Biol Chem
; 300(8): 107499, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38944125
ABSTRACT
Blood amino acid levels are maintained in a narrow physiological range. The pancreatic α cells have emerged as the primary aminoacidemia regulator through glucagon secretion to promote hepatic amino acid catabolism. Interruption of glucagon signaling disrupts the liver-α cells axis leading to hyperaminoacidemia, which triggers a compensatory rise in glucagon secretion and α cell hyperplasia. The mechanisms of hyperaminoacidemia-induced α cell hyperplasia remain incompletely understood. Using a mouse α cell line and in vivo studies in zebrafish and mice, we found that hyperaminoacidemia-induced α cell hyperplasia requires ErbB3 signaling. In addition to mechanistic target of rapamycin complex 1, another ErbB3 downstream effector signal transducer and activator of transcription 3 also plays a role in α cell hyperplasia. Mechanistically, ErbB3 may partner with ErbB2 to stimulate cyclin D2 and suppress p27 via mechanistic target of rapamycin complex 1 and signal transducer and activator of transcription 3. Our study identifies ErbB3 as a new regulator for hyperaminoacidemia-induced α cell proliferation and a critical component of the liver-α cells axis that regulates aminoacidemia.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pez Cebra
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Receptor ErbB-3
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Células Secretoras de Glucagón
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Ciclina D2
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Diana Mecanicista del Complejo 1 de la Rapamicina
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Hiperplasia
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
China