IGF-I Mediated Recruitment of Glucose Transporters from Intracellular Membranes to Plasma Membranes in L6 Muscle Cells
IGF-I has long been known to have mitogenic effects on isolated skeletal tissue (Salmon and Daughaday, 1957) and insulin-like metabolic effects on isolated adipose tissue and muscle tissue (Froesch et al., 1966; Poggi et al., 1979). Stimulation of glucose utilization by IGF-I has been observed in vivo in rats and humans (Zapf et al., 1986; Guler et al., 1987). Moreover, Giacca et al. (1990) have demonstrated that skeletal muscle is the preferred site for the stimulation of glucose utilization by IGF-I in completely insulin-deficient diabetic dogs. Simultaneously, Moxely III et al. (1990) demonstrated that in vivo, IGF-I stimulates hexose uptake directly into rat muscles. These specific effects of IGF-I on skeletal muscle are consistent with the observation that skeletal muscle expresses abundant amounts of IGF-I receptors (Livingston et al., 1988, Dohm et al., 1990), whereas adipose tissue has very low numbers of IGF-I receptors (Rechler and Nissley, 1985; Sinha et al., 1990). Skeletal muscle is also the primary site of action for the stimulation of glucose utilization by insulin in vivo (Defronzo et al., 1981). Although IGF-I and insulin have common biological actions, IGF-I and insulin receptors may function independently. For example, rat 1 fibroblasts expressing a mutant insulin receptor with an inactive tyrosine kinase are unresponsive to insulin stimulation of glucose uptake but can still respond to IGF-I through their endogenous IGF-I receptors (McClain et al., 1990). Secondly, Lammers et al. (1989) demonstrated that chimeric receptors consisting of the extracellular insulin receptor domain and the intracellular IGF-I receptor domain were ten times more responsive to insulin for stimulation of DNA synthesis than was the native insulin receptor. This suggested that the intracellular kinase of the IGF-I receptor is more active than the insulin receptor kinase and is thus inherently different from its insulin receptor counterpart. Hence, IGF-I and insulin and their receptors share common responses but can trigger them independently.
KeywordsInsulin Receptor Membrane Fraction Internal Membrane Plasma Membrane Fraction Plasma Membrane Marker
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