Differential Effects of Furin Deficiency on Insulin Receptor Processing and Glucose Control in Liver and Pancreatic ß Cells of Mice.
Int J Mol Sci
; 22(12)2021 Jun 14.
Article
en En
| MEDLINE
| ID: mdl-34198511
ABSTRACT
The insulin receptor (IR) is critically involved in maintaining glucose homeostasis. It undergoes proteolytic cleavage by proprotein convertases, which is an essential step for its activation. The importance of the insulin receptor in liver is well established, but its role in pancreatic ß cells is still controversial. In this study, we investigated the cleavage of the IR by the proprotein convertase FURIN in ß cells and hepatocytes, and the contribution of the IR in pancreatic ß cells and liver to glucose homeostasis. ß-cell-specific Furin knockout (ßFurKO) mice were glucose intolerant, but liver-specific Furin knockout (LFurKO) mice were normoglycemic. Processing of the IR was blocked in ßFurKO cells, but unaffected in LFurKO mice. Most strikingly, glucose homeostasis in ß-cell-specific IR knockout (ßIRKO) mice was normal in younger mice (up to 20 weeks), and only mildly affected in older mice (24 weeks). In conclusion, FURIN cleaves the IR non-redundantly in ß cells, but redundantly in liver. Furthermore, we demonstrated that the IR in ß cells plays a limited role in glucose homeostasis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptor de Insulina
/
Furina
/
Células Secretoras de Insulina
/
Glucosa
/
Hígado
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2021
Tipo del documento:
Article
País de afiliación:
Bélgica