Pancreatic Hormone Insulin Modulates Organic Anion Transporter 1 in the Kidney: Regulation via Remote Sensing and Signaling Network

Zhou Yu, Jinghui Zhang, Zhengxuan Liang, Jingjing Wu, Kexin Liu, Guofeng You

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Organic anion transporter 1 (OAT1) expressed in the kidney plays an important role in the elimination of numerous anionic drugs used in the clinic. We report here that insulin, a pancreas-secreted hormone, regulated the expression and activity of kidney-specific OAT1 both in cultured cells and in rats. We showed that treatment of OAT1-expressing cells with insulin led to an increase in OAT1 expression, transport activity, and SUMOylation. Such insulin-induced increase was blocked by afuresertib, a specific inhibitor for protein kinase B (PKB), suggesting insulin regulates OAT1 through PKB signaling pathway. Furthermore, insulin stimulated transport activity and SUMOylation of endogenously expressed OAT1 in rat kidneys. In conclusion, our data support a remote sensing and signaling model, in which OAT1 plays an essential role in intercellular and inter-organ communication and in maintaining local and whole-body homeostasis. Such complex and dedicated communication is carried out by insulin, and PKB signaling and membrane sorting. Graphical Abstract: [Figure not available: see fulltext.].

Original languageEnglish (US)
Article number13
JournalAAPS Journal
Volume25
Issue number1
DOIs
StatePublished - Feb 2023

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Drug transporter
  • Insulin
  • Organic anion transporter
  • Protein kinase B
  • Regulation
  • SUMOylation

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