biostudies-literatureUnknown90Rada PCenter for Networked Biomedical Research on Neurodegenerative DiseasesCarlos III Health InstituteMinisterio de Ciencia e InnovaciónBiomedical Research Network Centre of Diabetes and Associated Metabolic DiseasesCommunity of Madrid<h4>Objectives</h4>Protein kinase D (PKD) family is emerging as relevant regulator of metabolic homeostasis. However, the precise role of PKD2 in modulating hepatic insulin signaling has not been fully elucidated and it is the aim of this study.<h4>Methods</h4>PKD inhibition was analyzed for insulin signaling in mouse and human hepatocytes. PKD2 was overexpressed in Huh7 hepatocytes and mouse liver, and insulin responses were evaluated. Mice with hepatocyte-specific PKD2 depletion (PKD2^ΔHep) and PKD2^fl/fl mice were fed a chow (CHD) or high fat diet (HFD) and glucose homeostasis and lipid metabolism were investigated.<h4>Results</h4>PKD2 silencing enhanced insulin signaling in hepatocytes, an effect also found in primary hepatocytes from PKD2^ΔHep mice. ConveMolecular metabolism102045https://www.ebi.ac.uk/biostudies/studies/S-EPMC11535753biostudies-literatureProtein kinase D2 modulates hepatic insulin sensitivity in male mice.PMC11535753Sabio GCarceller-Lopez EFernandez-Hernandez CHitos ABGomez-Santos BAspichueta PRada PPose-Utrilla JIglesias TValverde AMRey EGarcia AGonzalez-Rodriguez AGarcia-Monzon CfalseProtein kinase D2 modulates hepatic insulin sensitivity in male mice.<h4>Objectives</h4>Protein kinase D (PKD) family is emerging as relevant regulator of metabolic homeostasis. However, the precise role of PKD2 in modulating hepatic insulin signaling has not been fully elucidated and it is the aim of this study.<h4>Methods</h4>PKD inhibition was analyzed for insulin signaling in mouse and human hepatocytes. PKD2 was overexpressed in Huh7 hepatocytes and mouse liver, and insulin responses were evaluated. Mice with hepatocyte-specific PKD2 depletion (PKD2^ΔHep) and PKD2^fl/fl mice were fed a chow (CHD) or high fat diet (HFD) and glucose homeostasis and lipid metabolism were investigated.<h4>Results</h4>PKD2 silencing enhanced insulin signaling in hepatocytes, an effect also found in primary hepatocytes from PKD2^ΔHep mice. Conve2024-01-01T00:00:00Z2024 Dec2026-07-16T13:19:54.785Z2025-04-04T18:54:24.628ZS-EPMC115357533940161410.1016/j.molmet.2024.102045