IGF-I AND INSULIN REGULATE GLUCOSE-TRANSPORT IN MOUSE BLASTOCYSTS VIAIGF-I RECEPTOR

The roles of glucose deprivation, insulin, and insulin-like growth fac tor I (IGF-I) in the regulation of glucose transport in the mouse blas tocyst were examined. Glucose transport, measured by uptake of 3-O-met hyl glucose (3-OMG), was increased by 19% (P < 0.01) in response to gl ucose deprivation. Both IGF-I and insulin stimulated uptake, but IGF-I was 1,000-fold more potent than insulin, increasing uptake by 51% at 1.7 pM (P < 0.001). These effects began to appear after 20 min of incu bation with growth factors, and required the simultaneous presence of glucose. The relative potencies of insulin and IGF-I suggest that the actions of IGF-I and insulin were both mediated via the IGF-I receptor . The inactivity of a specific agonistic insulin receptor antibody (B1 0) confirms this and suggests that this action may be independent of s ignalling through IRS-1. Cycloheximide decreased growth factor-stimula ted transport by about 40%, indicating that both protein synthesis and transporter recruitment from cytoplasmic stores are responsible for m aximal stimulation. These characteristics are consistent with GLUT1-fa cilitated glucose uptake and suggest that GLUT1 is the regulatable tra nsporter in mouse blastocysts. Stimulation of GLUT1 may be a ubiquitou s feature of the autocrine/paracrine activity of IGF-I in cell growth and proliferation. (C) 1996 Wiley-Liss, Inc.