AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice View Full Text


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Article Info

DATE

2021-01-08

AUTHORS

Masato Iwabu, Miki Okada-Iwabu, Hiroaki Tanabe, Nozomi Ohuchi, Keiko Miyata, Toshiko Kobori, Sara Odawara, Yuri Kadowaki, Shigeyuki Yokoyama, Toshimasa Yamauchi, Takashi Kadowaki

ABSTRACT

Adiponectin receptors, AdipoR1 and AdipoR2 exert anti-diabetic effects. Although muscle-specific disruption of AdipoR1 has been shown to result in decreased insulin sensitivity and decreased exercise endurance, it remains to be determined whether upregulation of AdipoR1 could reverse them in obese diabetic mice. Here, we show that muscle-specific expression of human AdipoR1 increased expression levels of genes involved in mitochondrial biogenesis and oxidative stress-detoxification to almost the same extents as treadmill exercise, and concomitantly increased insulin sensitivity and exercise endurance in obese diabetic mice. Moreover, we created AdipoR-humanized mice which express human AdipoR1 in muscle of AdipoR1·R2 double-knockout mice. Most importantly, the small-molecule AdipoR agonist AdipoRon could exert its beneficial effects in muscle via human AdipoR, and increased insulin sensitivity and exercise endurance in AdipoR-humanized mice. This study suggests that expression of human AdipoR1 in skeletal muscle could be exercise-mimetics, and that AdipoRon could exert its beneficial effects via human AdipoR1. More... »

PAGES

45

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    URI

    http://scigraph.springernature.com/pub.10.1038/s42003-020-01579-9

    DOI

    http://dx.doi.org/10.1038/s42003-020-01579-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1134426654

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33420419


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