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BRL37344 stimulates...
BRL37344 stimulates GLUT4 translocation and glucose uptake in skeletal muscle via beta(2)-adrenoceptors without causing classical receptor desensitization
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Mukaida, Saori (författare)
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Sato, Masaaki (författare)
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- Öberg, Anette I. (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Dehvari, Nodi (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Olsen, Jessica M. (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Kocan, Martina (författare)
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Halls, Michelle Louise (författare)
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Merlin, Jon (författare)
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- Sandström, Anna L. (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Csikasz, Robert (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Evans, Bronwyn Anne (författare)
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Summers, Roger James (författare)
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Hutchinson, Ana Sabine (författare)
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- Bengtsson, Tore (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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(creator_code:org_t)
- American Physiological Society, 2019
- 2019
- Engelska.
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 316:5, s. R666-R677
- Relaterad länk:
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https://journals.phy...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The type 2 diabetes epidemic makes it important to find insulinin-dependent ways to improve glucose homeostasis. This study examines the mechanisms activated by a dual beta(2)-/beta(3)-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, beta(2)-adrenoceptor desensitization, beta-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 tolerance tests and in vivo and ex vivo skeletal muscle glucose uptake). In L6 cells, BRL37344 increased GLUT4 translocation and glucose uptake only by activation of beta(2)-adrenoceptors, with a similar potency and efficacy to that of the nonselective beta-adrenoceptor agonist isoprenaline, despite being a partial agonist with respect to cAMP generation. GLUT4 translocation occurred independently of Akt and AMPK phosphorylation but was dependent on mTORC2. Furthermore, in contrast to isoprenaline, BRL37344 did not promote agonist-mediated desensitization and failed to recruit beta-arrestin1/2 to the beta(2)-adrenoceptor. In conclusion, BRL37344 improved glucose tolerance and increased glucose uptake into skeletal muscle in vivo and ex vivo through a beta(2)-adrenoceptor-mediated mechanism independently of Akt. BRL37344 was a partial agonist with respect to cAMP, but a full agonist for glucose uptake, and importantly did not cause classical receptor desensitization or internalization of the receptor.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- beta(2)-adrenoceptor
- beta-arrestin
- BRL37344
- glucose uptake
- GLUT4
- isoprenaline
- receptor desensitization
- skeletal muscle
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Mukaida, Saori
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Sato, Masaaki
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Öberg, Anette I.
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Dehvari, Nodi
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Olsen, Jessica M ...
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Kocan, Martina
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visa fler...
-
Halls, Michelle ...
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Merlin, Jon
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Sandström, Anna ...
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Csikasz, Robert
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Evans, Bronwyn A ...
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Summers, Roger J ...
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Hutchinson, Ana ...
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Bengtsson, Tore
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visa färre...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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American Journal ...
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Stockholms universitet