Liver-specific ablation of insulin-degrading enzyme causes hepatic insulin resistance and glucose intolerance, without affecting insulin clearance in mice.

ABSTRACT: The role of insulin-degrading enzyme (IDE), a metalloprotease with high affinity for insulin, in insulin clearance remains poorly understood.

Objective

This study aimed to clarify whether IDE is a major mediator of insulin clearance, and to define its role in the etiology of hepatic insulin resistance.

Methods

We generated mice with liver-specific deletion of Ide (L-IDE-KO) and assessed insulin clearance and action.

Results

L-IDE-KO mice exhibited higher (~20%) fasting and non-fasting plasma glucose levels, glucose intolerance and insulin resistance. This phenotype was associated with ~30% lower plasma membrane insulin receptor levels in liver, as well as ~55% reduction in insulin-stimulated phosphorylation of the insulin receptor, and its downstream signaling molecule

SUBMITTER: Villa-Perez P 

PROVIDER: S-EPMC6185772 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature