Rutin potentiates calcium uptake via voltage-dependent calcium channel associated with stimulation of glucose uptake in skeletal muscle

• Published in: Archives of biochemistry and biophysics Vol. 532; no. 2; pp. 55 - 60
• Main Authors: Kappel, Virginia Demarchi, Zanatta, Leila, Postal, Bárbara Graziela, Silva, Fátima Regina Mena Barreto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.04.2013
• Subjects: Animals; Antioxidants - pharmacology; Biological Transport - drug effects; calcium; Calcium - metabolism; calcium channels; Calcium Channels - metabolism; Calcium uptake; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; cAMP-dependent protein kinase; Diabetes; DNA; DNA - metabolism; drugs; glucose; Glucose - metabolism; Glucose uptake; homeostasis; Male; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; muscles; plasma membrane; Rats; Rats, Wistar; Rutin; Rutin - pharmacology; signal transduction; Signal Transduction - drug effects; skeletal muscle; Soleus muscle; therapeutics; Thymidine - metabolism; Glucose uptake; Diabetes; Rutin; Soleus muscle; Calcium uptake
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2013.01.008

[Display omitted] ► Rutin stimulates calcium uptake in soleus muscle. ► L-VDCC, CaMKII, MEK and PKA are involved in the signaling pathways of rutin. ► Calcium influences the stimulatory effect of rutin on DNA activity. ► Rutin induced-glucose uptake through CaMKII in soleus muscle. Rutin is a flavonoid with several pharmacological properties and it has been demonstrated that rutin can modulate glucose homeostasis. In skeletal muscle, an increase in intracellular calcium concentration may induce glucose transporter-4 (GLUT-4) translocation with consequent glucose uptake. The aim of this study was to investigate the effect of rutin and intracellular pathways on calcium uptake as well as the involvement of calcium in glucose uptake in skeletal muscle. The results show that rutin significantly stimulated calcium uptake through voltage-dependent calcium channels as well as mitogen-activated kinase (MEK) and protein kinase A (PKA) signaling pathways. Also, rutin stimulated glucose uptake in the soleus muscle and this effect was mediated by extracellular calcium and calcium–calmodulin-dependent protein kinase II (CaMKII) activation. In conclusion, rutin significantly stimulates calcium uptake in rat soleus muscles. Furthermore, the increase in intracellular calcium concentration is involved in DNA activation by rutin. Also, rutin-induced glucose uptake via CaMKII may result in GLUT-4 translocation to the plasma membrane, characterizing an insulin-independent pathway. These findings indicate that rutin is a potential drug candidate for diabetes therapy.