biostudies-literatureUnknown17(5)Zhang YNCATSNational Institute of Diabetes and Digestive and Kidney DiseasesNCINIGMS<h4>Background & aims</h4>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.<h4>Methods</h4>To do this, we generated mice expressing wild-type murine Arg2, enzymatically inactive Arg2 (Arg2^H160F) and Arg2 lacking itsCellular and molecular gastroenterology and hepatology801-820https://www.ebi.ac.uk/biostudies/studies/S-EPMC10966292biostudies-literatureA Structure-function Analysis of Hepatocyte Arginase 2 Reveals Mitochondrial Ureahydrolysis as a Determinant of Glucose Oxidation.PMC10966292Wasserman HDHiggins CBKelly SCAdams JAZhang YDeBosch BJSun JLantier LfalseA Structure-function Analysis of Hepatocyte Arginase 2 Reveals Mitochondrial Ureahydrolysis as a Determinant of Glucose Oxidation.<h4>Background & aims</h4>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.<h4>Methods</h4>To do this, we generated mice expressing wild-type murine Arg2, enzymatically inactive Arg2 (Arg2^H160F) and Arg2 lacking its2024-01-01T00:00:00Z2024 Jan2025-04-21T21:26:07.134Z2025-04-05T18:24:52.721ZS-EPMC109662923828054910.1016/j.jcmgh.2024.01.016