Do CB1 Cannabinoid Receptors Regulate Insulin Signalling

The purpose of this study was to investigate the expression and signalling of CB1 cannabinoid receptors and the impact of CB1 activation and inhibition upon insulin signalling in rat primary skeletal muscle cells. QRT-PCR (Taqman) identified CB1 cannabinoid receptor mRNA expression with Ct values of 26.5-27.5 in myoblasts, myotubes and skeletal muscle tissue. In cultured myotubes, forskolin (1 ?M)–evoked elevation of cAMP was unaltered in the presence of ACEA (10 nM) or rimonabant (100 nM) for 10 minutes. Treatment with ACEA (10 nM) for 10 minutes increased activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase (~400% and ~150%, respectively); these responses which were significantly inhibited by rimonabant (100 nM). Insulin (100 nM) treatment of myotubes for 10 minutes increased the activation of AKT/protein kinase B (870%), glycogen synthase kinase 3? and B (200% and 230%, respectively), ERK1/2 (400%) and p38 MAP kinase (500%); pre-treatment with ACEA (10nM) for 24 hours failed to alter these responses. AICAR (1 mM)-stimulated AMP activated protein kinase activity was also unaltered by ACEA. These findings provide evidence for expression of functionally active CB1 cannabinoid receptor in skeletal muscle. However, they fail to support previous reports suggesting an interaction between insulin and CB1 receptor signalling in these cells.