{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mayer AE"],"funding":["European Research Council","Deutsche Forschungsgemeinschaft","European Foundation for the Study of Diabetes"],"pagination":["eaav9150"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7612146"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(593)"],"pubmed_abstract":["Hepatic activation of protein kinase C (PKC) isoforms by diacylglycerol (DAG) promotes insulin resistance and contributes to the development of type 2 diabetes (T2D). The closely related protein kinase D (PKD) isoforms act as effectors for DAG and PKC. Here, we showed that PKD3 was the predominant PKD isoform expressed in hepatocytes and was activated by lipid overload. PKD3 suppressed the activity of downstream insulin effectors including the kinase AKT and mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2). Hepatic deletion of PKD3 in mice improved insulin-induced glucose tolerance. However, increased insulin signaling in the absence of PKD3 promoted lipogenesis mediated by SREBP (sterol regulatory element-binding protein) and consequently increased triglyceride and chol"],"journal":["Science signaling"],"pubmed_title":["The kinase PKD3 provides negative feedback on cholesterol and triglyceride synthesis by suppressing insulin signaling."],"pmcid":["PMC7612146"],"funding_grant_id":["SicMetabol","678119","HepatoMetaboPath","Su 820/1-1","683000"],"pubmed_authors":["Loza Valdes AE","Schulze A","Mayer AE","Erk M","Sumara G","Braun U","Heikenwalder M","El-Merahbi R","Zhang T","Viera JT","Schmitz W","Loffler MC","Leitges M"],"additional_accession":[]},"is_claimable":false,"name":"The kinase PKD3 provides negative feedback on cholesterol and triglyceride synthesis by suppressing insulin signaling.","description":"Hepatic activation of protein kinase C (PKC) isoforms by diacylglycerol (DAG) promotes insulin resistance and contributes to the development of type 2 diabetes (T2D). The closely related protein kinase D (PKD) isoforms act as effectors for DAG and PKC. Here, we showed that PKD3 was the predominant PKD isoform expressed in hepatocytes and was activated by lipid overload. PKD3 suppressed the activity of downstream insulin effectors including the kinase AKT and mechanistic target of rapamycin complex 1 and 2 (mTORC1 and mTORC2). Hepatic deletion of PKD3 in mice improved insulin-induced glucose tolerance. However, increased insulin signaling in the absence of PKD3 promoted lipogenesis mediated by SREBP (sterol regulatory element-binding protein) and consequently increased triglyceride and chol","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Aug","modification":"2025-04-18T22:45:37.146Z","creation":"2022-02-11T14:16:24.585Z"},"accession":"S-EPMC7612146","cross_references":{"pubmed":["31387939"],"doi":["10.1126/scisignal.aav9150"]}}