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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 and Ahuja, KDK and Beckett, JM and Myers, S, TRPV1 activation by capsaicin mediates glucose oxidation and ATP production independent of insulin signalling in mouse skeletal muscle cells, Cells, 10, (6) Article 1560. ISSN 2073-4409 (2021) [Refereed Article]

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Copyright Statement

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 (

DOI: doi:10.3390/cells10061560


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 Details

Item Type:Refereed Article
Keywords:capsaicin, TRPV1, CAMKK2, ERK1/2, glucose oxidation, ATP, skeletal muscle
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Vahidi Ferdowsi, P (Ms Parisa Vahidi Ferdowsi)
UTAS Author:Ahuja, KDK (Dr Kiran Ahuja)
UTAS Author:Beckett, JM (Dr Jeff Beckett)
UTAS Author:Myers, S (Dr Stephen Myers)
ID Code:145250
Year Published:2021
Web of Science® Times Cited:9
Deposited By:Health Sciences
Deposited On:2021-07-13
Last Modified:2022-08-19
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