title: Nucleobindin-2 is a positive regulator for insulin-stimulated glucose transporter 4 translocation in fenofibrate treated E11 podocytes.
abstract: The physiology of insulin signaling under normal and disease conditions is well studied in classical insulin target tissues, but not in podocytes. To examine insulin stimulation of podocyte GLUT4 translocation, we established a protocol involving treatment with the PPARα agonist fenofibrate to induce E11 podocyte differentiation within 48 hours rather than 7-10 days, which is required for differentiation under the reported protocol. This allowed us to transiently introduce GLUT4 reporter cDNA and RNAi and thereby to examine the regulatory pathway involved. Here we demonstrate that treatment with 200 μM fenofibrate for 36 hours following transfection had a dramatic effect on podocyte morphology, induced several podocyte specific protein expression markers (G protein-coupled receptor 137B, chloride intracellular channel 5, and nephrin) and resulted in insulin-stimulated GLUT4 translocation. In addition, Nucleobindin-2 was found to constitutively associate with Septin 7 (the repressor of GLUT4 translocation), and knockdown of Nucleobindin-2 was found to completely abrogate insulin-stimulated GLUT4 translocation. Together, these data suggest that Nucleobindin-2 may repress Septin7-induced inhibition of insulin-stimulated GLUT4 translocation in podocytes.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Tsugumichi
authors.initials: T
authors.lastname: Saito
authors.forename: Eijiro
authors.initials: E
authors.lastname: Yamada
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimoda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tagaya
authors.forename: Koshi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Satoh
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.forename: Junichi
authors.initials: J
authors.lastname: Okada
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Pessin
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D011345:Fenofibrate / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D000080866:Nucleobindins; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism; D058112:Septins / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; C495693:Slc2a4 protein, mouse; C512895:Sept7 protein, mouse; D058112:Septins; D011345:Fenofibrate