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

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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.

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All data generated and analysed in this study are included in this published article.

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Acknowledgements

We would like to thank Dr. Vanessa Routh from Rutgers University New Jersey Medical School (Newark, NJ, USA) for her guidance on rat in vivo study.

Funding

This work was supported by grants (to Dr. Guofeng You) from the National Institute of General Medical Sciences [R01-GM079123 and R01-GM097000].

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Authors and Affiliations

  1. Department of Pharmaceutics, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA

    Zhou Yu, Jinghui Zhang, Zhengxuan Liang & Guofeng You

  2. College of Pharmacy, Dalian Medical University, Dalian, China

    Jingjing Wu & Kexin Liu

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  1. Zhou Yu
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Contributions

Zhou Yu: project design, performing experiments, data analysis, manuscript writing; Jinghui Zhang: project design, methodology establishment, supervision; Zhengxuan Liang: performing experiments, data analysis; Jingjing Wu and Kexin Liu: guidance on optimizing conditions for kidney slice preparation; Guofeng You: project design, methodology establishment, manuscript writing, supervision. All authors have approved this version of the manuscript.

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Correspondence to Guofeng You.

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Yu, Z., Zhang, J., Liang, Z. et al. Pancreatic Hormone Insulin Modulates Organic Anion Transporter 1 in the Kidney: Regulation via Remote Sensing and Signaling Network. AAPS J 25, 13 (2023). https://doi.org/10.1208/s12248-022-00778-y

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