Drug development research for novel adiponectin receptor-targeted antidiabetic drugs contributing to healthy longevity View Full Text


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Article Info

DATE

2019-09-19

AUTHORS

Miki Okada-Iwabu, Masato Iwabu, Toshimasa Yamauchi, Takashi Kadowaki

ABSTRACT

It is well recognized that the decrease of adiponectin associated with high-fat diet and lack of exercise accounts for the onset of insulin resistance, type 2 diabetes, the metabolic syndrome, and cardiovascular disease. Our research efforts have led to the identification of adiponectin receptors, AdipoR1 and AdipoR2, with the former shown to activate AMP kinase in the liver and the latter shown to activate peroxisome proliferator-activated receptor-α signaling thereby increasing fatty acid oxidation. Again, adiponectin upregulates mitochondrial function in the skeletal muscle thereby improving glucose/lipid metabolism and insulin resistance. These findings suggested that activation of adiponectin/AdipoR signaling could represent a viable therapeutic approach to lifestyle-linked diseases associated with prevalent obesity thus contributing to healthy longevity in humans. Indeed, they have led to the successful discovery of AdipoRon, a small-molecule AdipoR-activating compound. Thus far, AdipoRon has been found not only to improve insulin resistance in mice but to prolong their lifespan shortened by high-fat diet. Additionally, our structure-based drug discovery research has led to AdipoR being identified as an entirely novel structure having a zinc iron bound within its seven-transmembrane domain as well as an opposite orientation to that of G protein-coupled receptors. It is expected that increasing insight into AdipoR signaling will facilitate the structure-based optimization of candidate small-molecule AdipoR-activating compounds for human use as well as the development of molecularly targeted and calorie-limiting/exercise-mimicking agents for lifestyle-linked diseases. More... »

PAGES

237-244

References to SciGraph publications

  • 2000-05. Triglycerides and toggling the tummy in NATURE GENETICS
  • 2002-06-17. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 in NATURE MEDICINE
  • 2015-01-10. Expression, purification, crystallization, and preliminary X-ray crystallographic studies of the human adiponectin receptors, AdipoR1 and AdipoR2 in JOURNAL OF STRUCTURAL AND FUNCTIONAL GENOMICS
  • 2010-04-01. Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1 in NATURE
  • 2013-10-30. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity in NATURE
  • 2007-02-01. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions in NATURE MEDICINE
  • 2015-12-03. Adiponectin/adiponectin receptor in disease and aging in NPJ AGING
  • 2011-02-16. Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB in NATURE
  • 1998-06. Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons in NATURE GENETICS
  • 1994-12. Positional cloning of the mouse obese gene and its human homologue in NATURE
  • 2017-03-22. Structural insights into adiponectin receptors suggest ceramidase activity in NATURE
  • 2006-01. The humoral side of insulin resistance in NATURE MEDICINE
  • 2001-08-01. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action in NATURE MEDICINE
  • 2003-06. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects in NATURE
  • 2015-04-08. Crystal structures of the human adiponectin receptors in NATURE
  • 2000-02. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase in NATURE
  • 2002-10-07. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase in NATURE MEDICINE
  • 2001-08-01. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity in NATURE MEDICINE
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    http://scigraph.springernature.com/pub.10.1007/s13340-019-00409-6

    DOI

    http://dx.doi.org/10.1007/s13340-019-00409-6

    DIMENSIONS

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