title: Reduced DPP4 activity improves insulin signaling in primary human adipocytes.
abstract: DPP4 is a ubiquitously expressed cell surface protease which is also released to the circulation as soluble DPP4 (sDPP4). Recently, we identified DPP4 as a novel adipokine oversecreted in obesity and thus potentially linking obesity to the metabolic syndrome. Furthermore, sDPP4 impairs insulin signaling in an autocrine and paracrine fashion in different cell types. However, it is still unknown which functional role DPP4 might play in adipocytes. Therefore, primary human adipocytes were treated with a specific DPP4 siRNA. Adipocyte differentiation was not affected by DPP4 silencing. Interestingly, DPP4 reduction improved insulin responsiveness of adipocytes at the level of insulin receptor, proteinkinase B (Akt) and Akt substrate of 160 kDa. To investigate whether the observed effects could be attributed to the enzymatic activity of DPP4, human adipocytes were treated with the DPP4 inhibitors sitagliptin and saxagliptin. Our data show that insulin-stimulated activation of Akt is augmented by DPP4 inhibitor treatment. Based on our previous observation that sDPP4 induces insulin resistance in adipocytes, and that adipose DPP4 levels are higher in obese insulin-resistant patients, we now suggest that the abundance of DPP4 might be a regulator of adipocyte insulin signaling.
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Röhrborn
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Brückner
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Sell
authors.affiliation: Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany. Electronic address: eckel@uni-duesseldorf.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Eckel
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives; D017667:Adipocytes / Q000166:cytology* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004151:Dipeptides / Q000008:administration & dosage; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage; D004789:Enzyme Activation; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; C502994:saxagliptin; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000218:Adamantane; D000068900:Sitagliptin Phosphate
keywords: DPP4; DPP4 inhibition; Insulin signaling; Primary human adipocytes; siRNA-mediated silencing