IGF-I and insulin regulate glucose transport in mouse blastocysts via IGF-I receptor.

The roles of glucose deprivation, insulin, and insulin-like growth factor I (IGF-I) in the regulation of glucose transport in the mouse blastocyst were examined. Glucose transport, measured by uptake of 3-0-methyl glucose (3-OMG), was increased by 19% (P < 0.01) in response to glucose 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 incubation 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 (B10) confirms this and suggests that this action may be independent of signalling through IRS-1. Cycloheximide decreased growth factor-stimulated transport by about 40%, indicating that both protein synthesis and transporter recruitment from cytoplasmic stores are responsible for maximal stimulation. These characteristics are consistent with GLUT1-facilitated glucose uptake and suggest that GLUT1 is the regulatable transporter in mouse blastocysts. Stimulation of GLUT1 may be a ubiquitous feature of the autocrine/ paracrine activity of IGF-I in cell growth and proliferation.