Abstract

Objective: The endogenous cannabinoid (or endocannabinoid) system (ECS) is part of a central neuromodulatory system thought to play a key role in the regulation of feeding behaviour and energy balance. However, increasing evidence suggests that modulation of the ECS may also act to regulate peripheral mechanisms involved in these processes, including lipogenesis in adipose tissue and liver, insulin release from pancreatic β-cells and glucose uptake into skeletal muscle. It was recently shown that cannabinoid receptor type 1 (CB1) and type 2 (CB2), both key components of the ECS, are expressed in human and rodent skeletal muscle. However, their role in modulating insulin sensitivity in this metabolically active tissue has yet to be determined. Our aim was to establish the role, if any, of these receptors in modulating insulin sensitivity in skeletal muscle cells.

Research Design And Methods: Cultured skeletal muscle cells were exposed to CB1 and/or CB2 pharmacological agonists/antagonists/inverse agonists and the resulting effects on insulin-regulated PI3K-PKB and ERK1/2-directed signalling were determined.

Results: Here, we report that modulating the activity of the ECS in skeletal muscle regulates both insulin-dependent MAP Kinase (ERK1/2) and the canonical PI3K-PKB signalling pathways. We show that pharmacological activation or inhibition of CB1 receptor activity exerts a differential effect with regards to MAP Kinase and PKB-directed signalling.

Conclusions: Our study provides evidence that signalling via cannabinoid receptors can significantly modulate mitogenic and metabolic signalling in skeletal muscle with important implications for muscle growth and differentiation as well as the regulation of glucose and lipid metabolism.