ATP8B1 Deficiency Causes Phosphodiesterase 4-Mediated Glucagon Resistance and Impaired Gluconeogenesis in Mouse and Human Liver.

ABSTRACT:

Background and aims

Deficiency of the phospholipid transporter ATP8B1 causes infantile-onset progressive familial intrahepatic cholestasis type I (PFIC1). Pre-transplant PFIC1 patients often present with mild dyslipidaemia. This raises the possibility that PFIC1 patients, besides cholestasis, may also experience defects in glucose and lipid metabolism. In this study, we aimed to investigate the role of ATP8B1 in hepatic glucose and lipid metabolism using the Atp8b1^G308V/G308V mutant mouse, a pre-clinical model of PFIC1.

Methods

Atp8b1^G308V/G308V and wild-type mice on normal chow were examined. Hepatic glucose metabolism was evaluated by oral glucose tolerance testing, quantification of fasting plasma glucose, insulin and lipids. Mechanistic studies were

SUBMITTER: Chang JC 

PROVIDER: S-EPMC12375944 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature