The role of phosphoinositide 3-kinase in insulin signalling

Abstract Introduction Muscle and adipose tissue play a central role in the maintenance of glucose homeostasis as they account for the majority of insulin-mediated glucose disposal in the post-prandial state. In obese and diabetic subjects, resistance to the stimulatory effects of insulin on glucose disposal into muscle and fat are instrumental in the development of the chronic hyperglycaemic state associated with these conditions. Studies using a range of techniques including nuclear magnetic resonance studies (Rothman et al. 1992), in vivo forearm perfusion studies (Yki-Jarvinen et al. 1990), indirect calorimetry (Butler et al. 1990) and biochemical assays in isolated muscle strips (Dohm et al. 1988, Andreasson et al. 1991) have demonstrated that the insulin resistance appears to be due to the additive effects of defects in multiple aspects of insulin action in muscle. These investigations have identified defects at the level of insulin stimulation of glucose transport across the plasma membrane as