A Structure-function Analysis of Hepatocyte Arginase 2 Reveals Mitochondrial Ureahydrolysis as a Determinant of Glucose Oxidation.

ABSTRACT:

Background & aims

Restoring hepatic and peripheral insulin sensitivity is critical to prevent or reverse metabolic syndrome and type 2 diabetes. Glucose homeostasis comprises in part the complex regulation of hepatic glucose production and insulin-mediated glucose uptake and oxidation in peripheral tissues. We previously identified hepatocyte arginase 2 (Arg2) as an inducible ureahydrolase that improves glucose homeostasis and enhances glucose oxidation in multiple obese, insulin-resistant models. We therefore examined structure-function determinants through which hepatocyte Arg2 governs systemic insulin action and glucose oxidation.

Methods

To do this, we generated mice expressing wild-type murine Arg2, enzymatically inactive Arg2 (Arg2^H160F) and Arg2 lacking its

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC10966292 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature