Capsaicin and Zinc Promote Glucose Uptake in C2C12 Skeletal Muscle Cells through a Common Calcium Signalling Pathway

• Published in: International journal of molecular sciences Vol. 23; no. 4; p. 2207
• Main Authors: Ferdowsi, Parisa Vahidi, Ahuja, Kiran D K, Beckett, Jeffrey M, Myers, Stephen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17-02-2022; MDPI
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Benzimidazoles - pharmacology; Ca2+/calmodulin-dependent protein kinase; Calcium; Calcium - metabolism; Calcium Signaling - drug effects; Calcium signalling; Calcium-binding protein; Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Calmodulin; CAMKK2; Capsaicin; Capsaicin - pharmacology; Carbohydrate Metabolism - drug effects; Carbohydrates; Cell activation; Cell Line; CREB; Cyclic AMP response element-binding protein; Diabetes; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Food; Gene expression; Glucose; Glucose - metabolism; Homeostasis; Insulin resistance; Intracellular signalling; Junb; Metabolic disorders; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscles; Musculoskeletal system; Naphthalimides - pharmacology; Nr4a3; Phosphorylation; Phosphorylation - drug effects; Plasma; Proteins; Rapamycin; Signal transduction; Skeletal muscle; TOR protein; TORC1; Transcription factors; Zinc - pharmacology; cAMP signalling; TORC1; CREB; calcium flux; Junb; Nr4a3; glucose metabolism; CAMKK2
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23042207

Capsaicin and zinc have recently been highlighted as potential treatments for glucose metabolism disorders; however, the effect of these two natural compounds on signalling pathways involved in glucose metabolism is still uncertain. In this study, we assessed the capsaicin- or zinc- induced activation of signalling molecules including calcium/calmodulin-dependent protein kinase 2 (CAMKK2), cAMP-response element-binding protein (CREB), and target of rapamycin kinase complex 1 (TORC1). Moreover, the expression status of genes associated with the control of glucose metabolism was measured in treated cells. The activation of cell signalling proteins was then evaluated in capsaicin- or zinc treated cells in the presence or absence of cell-permeant calcium chelator (BAPTA-AM) and the CAMKK inhibitor (STO-609). Finally, capsaicin- and zinc-induced glucose uptake was measured in the cells pre-treated with or without BAPTA-AM. Our results indicate that calcium flux induced by capsaicin or zinc led to activation of calcium signalling molecules and promoting glucose uptake in skeletal muscle cells. Pharmacological inhibition of CAMKK diminished activation of signalling molecules. Moreover, we observed an increase in intracellular cAMP levels in the cells after treatment with capsaicin and zinc. Our data show that capsaicin and zinc mediate glucose uptake in C2C12 skeletal muscle cells through the activation of calcium signalling.