Intracellular signalling mechanisms regulating glucose transport in insulin-sensitive tissues

The rate of glucose transport into cells is of fundamental importance in wh ole body homeostasis and adaptation to metabolic stresses, and this review examines the signalling mechanisms controlling this process. The events tha t mediate the action of insulin on glucose transport, which is by far the b est characterized paradigm for glucose transport regulation, are discussed. There are several excellent reviews on various aspects of this subject, wh ich are referred to while highlighting very recent developments in the fiel d, including the recently described CAP pathway, and emerging mechanisms fo r feedback regulation of insulin signalling. The manner in which hormonal s ignalling is modulated by stimuli such as oxidative and osmotic stress is t hen discussed. The second major physiological event where glucose transport regulation is critical is the contraction of skeletal muscle, due to the l arge metabolic demands of this activity. The mechanism of this regulation i s distinct from that initiated by insulin, and recent developments will be examined that have begun to clarify how contraction stimulates glucose tran sport in skeletal muscle, including the roles performed by AMP-activated pr otein kinase and nitric oxide synthase.