TRPV1 Activation by Capsaicin Mediates Glucose Oxidation and ATP Production Independent of Insulin Signalling in Mouse Skeletal Muscle Cells.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Adenosine Triphosphate/*metabolism ; Capsaicin/*pharmacology ; Glucose/*metabolism ; Insulin/*metabolism ; MAP Kinase Signaling System/*drug effects ; Muscle, Skeletal/*metabolism ; TRPV Cation Channels/*metabolism; Adenosine Triphosphate/genetics ; Insulin/genetics ; MAP Kinase Signaling System/genetics ; Oxidation-Reduction/drug effects ; TRPV Cation Channels/genetics ; Animals ; Cell Line ; Mice

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.

J Allergy Clin Immunol. 2014 Sep;134(3):714-721.e7. (PMID: 24948367)
Clin Nutr. 2016 Apr;35(2):388-393. (PMID: 25771490)
Front Endocrinol (Lausanne). 2017 Jan 24;8:6. (PMID: 28167928)
Adv Physiol Educ. 2014 Dec;38(4):308-14. (PMID: 25434013)
J Agric Food Chem. 2013 Mar 6;61(9):2096-102. (PMID: 23414078)
Mol Brain. 2021 Jan 19;14(1):15. (PMID: 33468207)
Am J Physiol Endocrinol Metab. 2015 Dec 15;309(12):E949-59. (PMID: 26487009)
Biochim Biophys Acta. 2010 Mar;1804(3):598-603. (PMID: 19770076)
Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E836-43. (PMID: 21771966)
Am J Physiol Cell Physiol. 2008 Sep;295(3):C836-43. (PMID: 18650261)
Diabetes. 2011 Mar;60(3):766-74. (PMID: 21282366)
Exp Mol Med. 2016 Jul 15;48(7):e245. (PMID: 27416781)
Expert Opin Ther Targets. 2008 Oct;12(10):1265-74. (PMID: 18781825)
Am J Physiol Endocrinol Metab. 2019 Oct 1;317(4):E667-E676. (PMID: 31408376)
Biochem Biophys Res Commun. 2013 Sep 13;439(1):66-70. (PMID: 23958300)
Chem Rev. 2001 Aug;101(8):2527-40. (PMID: 11749387)
Br J Pharmacol. 2013 May;169(1):69-81. (PMID: 23373714)
Cell Metab. 2014 Dec 2;20(6):939-52. (PMID: 25448702)
Mol Cell Biochem. 2018 Jun;443(1-2):11-23. (PMID: 29159769)
Int J Health Sci (Qassim). 2007 Jul;1(2):V-VIII. (PMID: 21475425)
Exp Mol Med. 2016 Apr 01;48:e224. (PMID: 27034026)
J Agric Food Chem. 2009 Dec 9;57(23):11148-53. (PMID: 19891501)
Front Physiol. 2017 Aug 25;8:602. (PMID: 28890700)
Eur J Pharmacol. 2005 Feb 21;509(2-3):211-7. (PMID: 15733558)
Semin Immunopathol. 2016 May;38(3):397-406. (PMID: 26403087)
J Biomed Biotechnol. 2010;2010:476279. (PMID: 20445742)
Am J Physiol Endocrinol Metab. 2016 Apr 15;310(8):E643-E651. (PMID: 26860984)
Curr Osteoporos Rep. 2019 Aug;17(4):169-177. (PMID: 31115859)
Diabetes. 2017 Jun;66(6):1432-1442. (PMID: 28533294)
Diabetes Metab J. 2013 Feb;37(1):1-21. (PMID: 23441028)
J Lipid Res. 2012 Dec;53(12):2490-514. (PMID: 22798688)
Int J Mol Sci. 2019 Apr 03;20(7):. (PMID: 30987128)
Mol Syst Biol. 2013 May 14;9:664. (PMID: 23670537)
Food Funct. 2020 Sep 23;11(9):7356-7370. (PMID: 32820787)
Phytother Res. 2001 Aug;15(5):391-4. (PMID: 11507729)
PLoS One. 2019 Jan 29;14(1):e0211420. (PMID: 30695053)
Exp Cell Res. 2005 Aug 15;308(2):291-9. (PMID: 15921682)
J Agric Food Chem. 2017 Mar 22;65(11):2323-2330. (PMID: 28230360)
Nutrients. 2018 May 17;10(5):. (PMID: 29772784)
Indian J Endocrinol Metab. 2016 Jul-Aug;20(4):546-51. (PMID: 27366724)
Curr Drug Targets. 2006 Nov;7(11):1435-41. (PMID: 17100583)
Diabetes. 2004 Feb;53(2):330-5. (PMID: 14747282)
Cells. 2014 May 23;3(2):517-45. (PMID: 24861977)
Am J Clin Nutr. 2006 Jul;84(1):63-9. (PMID: 16825682)
J Nutr Biochem. 2013 Jun;24(6):1078-85. (PMID: 23026494)
J Biol Chem. 2006 Aug 25;281(34):24149-60. (PMID: 16803904)
Front Pharmacol. 2019 Jan 23;10:6. (PMID: 30728775)
J Appl Physiol (1985). 2005 Dec;99(6):2181-8. (PMID: 16099889)
Front Endocrinol (Lausanne). 2018 Jul 31;9:420. (PMID: 30108548)
FASEB J. 2018 Apr;32(4):1741-1777. (PMID: 29242278)
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7531-6. (PMID: 19380737)
Int J Endocrinol. 2017;2017:4301461. (PMID: 29230243)
FASEB J. 2015 Aug;29(8):3182-92. (PMID: 25888600)
Sudan J Paediatr. 2017;17(2):11-20. (PMID: 29545660)
World J Diabetes. 2016 Sep 15;7(17):354-95. (PMID: 27660695)
J Biol Chem. 2004 Aug 27;279(35):36828-40. (PMID: 15199055)
PLoS One. 2018 Jan 26;13(1):e0191727. (PMID: 29373583)
Molecules. 2020 Nov 03;25(21):. (PMID: 33153045)
Int J Mol Sci. 2016 Dec 08;17(12):. (PMID: 27941647)
Circulation. 2020 Sep 15;142(11):1092-1105. (PMID: 32697107)
Cell Res. 2012 Mar;22(3):551-64. (PMID: 22184011)
Acta Physiol Scand. 2003 Aug;178(4):337-45. (PMID: 12864738)

190 Clifford Craig Foundation

Keywords: ATP; CAMKK2; ERK1/2; TRPV1; capsaicin; glucose oxidation; skeletal muscle

0 (Insulin)
0 (TRPV Cation Channels)
0 (TRPV1 protein, mouse)
8L70Q75FXE (Adenosine Triphosphate)
IY9XDZ35W2 (Glucose)
S07O44R1ZM (Capsaicin)

Date Created: 20210702 Date Completed: 20211026 Latest Revision: 20211026

20260130

PMC8234135

10.3390/cells10061560

34205555