Disruption of the phosphate transporter Pit1 in hepatocytes improves glucose metabolism and insulin signalling by modulating the USP7/IRS1 interaction.

ABSTRACT: The liver plays a central role in whole-body lipid and glucose homeostasis. Increasing dietary fat intake results in increased hepatic fat deposition, which is associated with a risk for development of insulin resistance and type 2 diabetes. In this study, we demonstrate a role for the phosphate inorganic transporter 1 (PiT1/SLC20A1) in regulating metabolism. Specific knockout of Pit1 in hepatocytes significantly improved glucose tolerance and insulin sensitivity, enhanced insulin signalling, and decreased hepatic lipogenesis. We identified USP7 as a PiT1 binding partner and demonstrated that Pit1 deletion inhibited USP7/IRS1 dissociation upon insulin stimulation. This prevented IRS1 ubiquitination and its subsequent proteasomal degradation. As a consequence delayed insulin negative feedba

ORGANISM(S): Mus musculus

SUBMITTER: Nicolas Cagnard 

PROVIDER: E-MTAB-4989 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress