Xenopus laevis oocytes possess a glucose transport system that is activated 3-to 5-fold by insulin-like growth factor I (Ka = 3 nM) and insulin (K. = 200-250 nM), properties suggesting activation mediated by an insulin-like growth factor I receptor. This activation increases the V.,,, of hexose uptake and has little or no effect on the Km for deoxyglucose (Km = 1-2 mM). Activation by hormone requires about 60 min and is inhibited by cytochalasin B but not by cycloheximide. The dependence of hexose uptake rate on hexose concentration exhibits cooperativity with Hill coefficients of 1.8 and 1.4 for the basal and hormone-activated states, respectively. Microuiijection of a monoclonal antibody directed against the tyrosine kinase domain of the human insulin receptor blocks activation of hexose uptake by insulin-like growth factor I and insulin but has no effect on basal uptake. Taken together the results implicate the tyrosine-specific protein kinase activity of a cell-surface insulin-like growth factor I receptor in the activation of glucose transport in the Xenopus oocyte. The activation of glucose uptake by insulin occurs in only a few cell types, notably skeletal and heart muscle cells and adipocytes (1). Although the intervening steps in signal transmission from the cell-surface insulin receptor to the glucose transporter have not yet been characterized, several important facts have emerged. It has been established that binding of insulin to its receptor activates the intrinsic tyrosine-specific protein kinase within the cytoplasmic domain of the receptor (2). There is now ample evidence to implicate the receptor kinase in signal transmission to known end targets of insulin action, including the glucose transport system (3). It is also known (4, 5) that upon stimulation of adipocytes or muscle cells with insulin, the glucose transporter undergoes translocation from an intracellular storage site to the plasma membrane, thereby causing increased glucose uptake. These characteristics ofthe insulin-stimulated glucose transport system make investigation of the activation mechanism difficult in typical animal cells or in a cell-free system. A promising alternative cell-type with which to study the mechanism ofinsulin-stimulated glucose uptake would be the Xenopus oocyte. The large size of this cell makes it possible to microinject specific reagents that interrupt or activate signal transmission to the glucose transporter (or other end targets of insulin action) at points in the pathway beyond the cell-surface receptor. Baulieu and coworkers (6) have reported that insulin can mimic progesterone by inducing cell division in oocytes and that the response to insulin is most likely mediated through the insulin receptor. Insulin (but not progesterone) action on oocyte maturation is blocked by an anti-insulinreceptor antibody directed against the tyrosine kinase domain ofthe receptor's ,8-subunit (7). Other activities have also been shown to be affected by insulin or insulin-like growth factor I (IGF-I) in Xenopus oocytes, ...
