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TRPV1 activation by capsaicin mediates glucose oxidation and ATP production independent of insulin signalling in mouse skeletal muscle cells

Vahidi Ferdowsi, P, Ahuja, KDK ORCID: 0000-0002-0323-4692, Beckett, JM ORCID: 0000-0002-2911-0313 and Myers, S ORCID: 0000-0003-4793-3820 2021 , 'TRPV1 activation by capsaicin mediates glucose oxidation and ATP production independent of insulin signalling in mouse skeletal muscle cells' , Cells, vol. 10, no. 6 , pp. 1-16 , doi:

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Background: Insulin resistance (IR), a key characteristic of type 2 diabetes (T2DM), is manifested by decreased insulin-stimulated glucose transport in target tissues. Emerging research has highlighted transient receptor potential cation channel subfamily V member (TRPV1) activation by capsaicin as a potential therapeutic target for these conditions. However, there are limited data on the effects of capsaicin on cell signalling molecules involved in glucose uptake. Methods: C2C12 cells were cultured and differentiated to acquire the myotube phenotype. The activation status of signalling molecules involved in glucose metabolism, including 5’ adenosine monophosphate-activated protein kinase (AMPK), calcium/calmodulin-dependent protein kinase 2 (CAMKK2), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), protein kinase B (AKT), and src homology phosphatase 2 (SHP2), was examined. Finally, activation of CAMKK2 and AMPK, and glucose oxidation and ATP levels were measured in capsaicin-treated cells in the presence or absence of TRPV1 antagonist (SB-452533). Results: Capsaicin activated cell signalling molecules including CAMKK2 and AMPK leading to increased glucose oxidation and ATP generation independent of insulin in the differentiated C2C12 cells. Pharmacological inhibition of TRPV1 diminished the activation of CAMKK2 and AMPK as well as glucose oxidation and ATP production. Moreover, we observed an inhibitory effect of capsaicin in the phosphorylation of ERK1/2 in the mouse myotubes. Conclusion: Our data show that capsaicin-mediated stimulation of TRPV1 in differentiated C2C12 cells leads to activation of CAMKK2 and AMPK, and increased glucose oxidation which is concomitant with an elevation in intracellular ATP level. Further studies of the effect of TRPV1 channel activation by capsaicin on glucose metabolism could provide novel therapeutic utility for the management of IR and T2DM.

Item Type: Article
Authors/Creators:Vahidi Ferdowsi, P and Ahuja, KDK and Beckett, JM and Myers, S
Keywords: capsaicin, TRPV1, CAMKK2, ERK1/2, glucose oxidation, ATP, skeletal muscle
Journal or Publication Title: Cells
Publisher: MDPI AG
ISSN: 2073-4409
DOI / ID Number:
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Copyright: © 2021 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) license (

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