Nucleobindin-2 is a positive regulator for insulin-stimulated glucose transporter 4 translocation in fenofibrate treated E11 podocytes

Tsugumichi Saito, Eijiro Yamada, Shuichi Okada, Yoko Shimoda, Yuko Tagaya, Koshi Hashimoto, Tetsurou Satoh, Masatomo Mori, Junichi Okada, Jeffrey E. Pessin, Masanobu Yamada

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6 Scopus citations

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 200μM 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.

Original languageEnglish (US)
Pages (from-to)933-939
Number of pages7
JournalEndocrine Journal
Volume61
Issue number9
DOIs
StatePublished - Sep 1 2014

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Keywords

  • Glucose transporter 4 translocation
  • Insulin
  • Insulin resistance
  • Nucleobindin-2
  • Podocyte

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Saito, T., Yamada, E., Okada, S., Shimoda, Y., Tagaya, Y., Hashimoto, K., Satoh, T., Mori, M., Okada, J., Pessin, J. E., & Yamada, M. (2014). Nucleobindin-2 is a positive regulator for insulin-stimulated glucose transporter 4 translocation in fenofibrate treated E11 podocytes. Endocrine Journal, 61(9), 933-939. https://doi.org/10.1507/endocrj.EJ14-0330