IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-09911-6.html
   My bibliography  Save this article

Antidiabetic and cardiovascular beneficial effects of a liver-localized mitochondrial uncoupler

Author

Listed:
  • Naohide Kanemoto

    (Otsuka Pharmaceutical Co., Ltd.)

  • Takashi Okamoto

    (Otsuka Pharmaceutical Co., Ltd.)

  • Koji Tanabe

    (Otsuka Pharmaceutical Co., Ltd.)

  • Takahiro Shimada

    (Otsuka Pharmaceutical Co., Ltd.)

  • Hitomi Minoshima

    (Otsuka Pharmaceutical Co., Ltd.)

  • Yuya Hidoh

    (Otsuka Pharmaceutical Co., Ltd.)

  • Masashi Aoyama

    (Otsuka Pharmaceutical Co., Ltd.)

  • Takashi Ban

    (Otsuka Pharmaceutical Co., Ltd.)

  • Yusuke Kobayashi

    (Otsuka Pharmaceutical Co., Ltd.)

  • Hikaru Ando

    (Otsuka Pharmaceutical Co., Ltd.)

  • Yuki Inoue

    (Otsuka Pharmaceutical Co., Ltd.)

  • Motohiro Itotani

    (Otsuka Pharmaceutical Co., Ltd.)

  • Seiji Sato

    (Otsuka Pharmaceutical Co., Ltd.)

Abstract

Inducing mitochondrial uncoupling (mUncoupling) is an attractive therapeutic strategy for treating metabolic diseases because it leads to calorie-wasting by reducing the efficiency of oxidative phosphorylation (OXPHOS) in mitochondria. Here we report a safe mUncoupler, OPC-163493, which has unique pharmacokinetic characteristics. OPC-163493 shows a good bioavailability upon oral administration and primarily distributed to specific organs: the liver and kidneys, avoiding systemic toxicities. It exhibits insulin-independent antidiabetic effects in multiple animal models of type I and type II diabetes and antisteatotic effects in fatty liver models. These beneficial effects can be explained by the improvement of glucose metabolism and enhancement of energy expenditure by OPC-163493 in the liver. Moreover, OPC-163493 treatment lowered blood pressure, extended survival, and improved renal function in the rat model of stroke/hypertension, possibly by enhancing NO bioavailability in blood vessels and reducing mitochondrial ROS production. OPC-163493 is a liver-localized/targeted mUncoupler that ameliorates various complications of diabetes.

Suggested Citation

  • Naohide Kanemoto & Takashi Okamoto & Koji Tanabe & Takahiro Shimada & Hitomi Minoshima & Yuya Hidoh & Masashi Aoyama & Takashi Ban & Yusuke Kobayashi & Hikaru Ando & Yuki Inoue & Motohiro Itotani & Se, 2019. "Antidiabetic and cardiovascular beneficial effects of a liver-localized mitochondrial uncoupler," Nature Communications, Nature, vol. 10(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09911-6
    DOI: 10.1038/s41467-019-09911-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-09911-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-09911-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09911-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.