An adiponectin receptor agonist antibody stimulates glucose uptake and fatty-acid oxidation by activating AMP-activated protein kinase

Jung, Dokyung; Bucher, Felicitas; Ryu, Suyeon; Jeong, Jongwon; Lee, Beom Yong; Jeong, Youngtae; Kim, Minseok S.; Oh, Yong‐Seok; Baek, Moon‐Chang; Yoon, Jong Hyuk; Yea, Kyungmoo

doi:10.1016/j.cyto.2019.154863

Cited by 8 publications

(1 citation statement)

References 22 publications

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“…This is also the AdipoR agonist antibody with potential for use in humans. Previously, Fc fusion single chain antibodies (scFv-Fcs), which bind to the C-terminal peptide of AdipoR and increase AMPK phosphorylation, were obtained from phage libraries ( 30 ). Given the pharmacological issue with these scFv-Fcs, i.e., a decreased blood half-life as suggested by their daily dosing, however, it was ensured that the agonist antibody had a blood half-life of 75 hours (table S2) comparable to that of endogenous mouse IgG antibodies.…”

Section: Discussionmentioning

confidence: 99%

A monoclonal antibody activating AdipoR for type 2 diabetes and nonalcoholic steatohepatitis

Asahara,

Okada-Iwabu,

Iwabu

et al. 2023

Sci. Adv.

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Adiponectin receptors, AdipoR1 and AdipoR2 are promising targets for the prevention and treatment of metabolic diseases. In this study, we aimed to establish agonistic antibodies against AdipoR1 and AdipoR2 with a long enough half-life to provide a means of improving poor medication adherence associated with preclinical small-molecule AdipoR agonists or existing antidiabetic drugs. Monoclonal antibodies were obtained by immunizing AdipoR knockout mice with human AdipoR-expressing cells. Of the antibodies shown to bind to both, an agonist antibody was obtained, which exhibited adenosine 5′-monophosphate–activated protein kinase–activating properties such as adiponectin and was named AdipoR-activating monoclonal antibody (AdipoRaMab). AdipoRaMab ameliorated glucose intolerance in high-fat diet–fed mice, which was not observed in AdipoR1·AdipoR2 double knockout mice. AdipoRaMab exhibited anti-inflammatory and antifibrotic effects in the nonalcoholic steatohepatitis (NASH) model, indicating its therapeutic potential in diabetes and in NASH. In addition, the results of this study indicated that AdipoRaMab may exert therapeutic effects even in a once-monthly dosing regimen through its humanization.

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Section: Discussionmentioning

confidence: 99%