The role of Ca2+ and calmodulin in insulin signalling in mammalian skeletal muscle.

The role of Ca2+ in mediating effects of insulin on skeletal muscle has been widely debated. It is believed that in skeletal muscle Ca2+ has a permissive role, necessary but not of prime importance in mediating the stimulatory actions of insulin. In this review, we present evidence that insulin causes a localized increase in the concentration of Ca2+. Specifically, insulin induces a rise in near-membrane Ca2+ but not the bulk Ca2+ in the myoplasm. The rise in near-membrane Ca2+ is because of an influx through channels that can be blocked by L-type Ca2+ channel inhibitors. Calcium appears to exert some of its subsequent effects via calmodulin-dependent processes as calmodulin inhibitors block the translocation of glucose transporters and other enzymes as well as the insulin-stimulated increase in glucose transport.