Journal article

BRL37344 stimulates GLUT4 translocation and glucose uptake in skeletal muscle via beta(2)-adrenoceptors without causing classical receptor desensitization

Saori Mukaida, Masaaki Sato, Anette Oberg, Nodi Dehvari, Jessica M Olsen, Martina Kocan, Michelle Louise Halls, Jon Merlin, Anna L Sandstrom, Robert Csikasz, Bronwyn Anne Evans, Roger James Summers, Ana Sabine Hutchinson, Tore Bengtsson

AJP Regulatory Integrative and Comparative Physiology | AMER PHYSIOLOGICAL SOC | Published : 2019

Abstract

The type 2 diabetes epidemic makes it important to find insulin-independent ways to improve glucose homeostasis. This study examines the mechanisms activated by a dual β2-/β3-adrenoceptor agonist, BRL37344, to increase glucose uptake in skeletal muscle and its effects on glucose homeostasis in vivo. We measured the effect of BRL37344 on glucose uptake, glucose transporter 4 (GLUT4) translocation, cAMP levels, β2-adrenoceptor desensitization, β-arrestin recruitment, Akt, AMPK, and mammalian target of rapamycin (mTOR) phosphorylation using L6 skeletal muscle cells as a model. We further tested the ability of BRL37344 to modulate skeletal muscle glucose metabolism in animal models (glucose tole..

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Grants

Awarded by Australian Research Council Linkage International Fellowship


Awarded by National Health and Medical Research Council (NHMRC) CJ Martin Overseas Biomedical Fellowship


Awarded by NHMRC


Funding Acknowledgements

S. Mukaida was supported by a Monash University Postgraduate Award. M. Sato was supported by the Wenner-Gren Foundation, Australian Research Council Linkage International Fellowship LX0989791, and National Health and Medical Research Council (NHMRC) CJ Martin Overseas Biomedical Fellowship 606763. A. I. Oberg was supported by the Henning and Johan Throne-Holst Foundation. N. Dehvari was supported by the Swedish Society for Medical Research. J. Merlin was supported by a Monash University Postgraduate Award. R. J. Summers was supported by NHMRC Program Grant 519461. D. S. Hutchinson was supported by NHMRC Career Development Fellowship 545952. T. Bengtsson is supported by the Ventenskapsradet-Medicin (VR-M) from the Swedish Research Council, Stiftelsen Svenska Diabetesforbundets Forskningsfond, the Magnus Bergvall Foundation, and the Carl Tryggers Foundation.