Expression of rat glucose transporter-5 (GLUTS) is tightly regulated during development. Expression and activity are low throughout the suckling and weaning stages, but perfusion of the small intestinal lumen with fructose solutions during weaning precociously enhances GLUTS activity and expression, Little is known, however, about the signal transduction pathways involved in the substrate-induced precocious GLUT5 development. We found that wortmannin and LY-294002, inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) specifically inhibited the increase in fructose uptake rate and brush-border GLUTS protein abundance but not GLUT5 mRNA abundance. Perfusion of EGF, an activator of PI3-kinase, also resulted in a marked wortmannin-inhibitable increase in fructose uptake. Perfusion of fructose for 4 h increased cytosolic immunostaining of phosphatidylinositol-3,4,5-triphosphate (PIP 3), the primary product of PI3-kinase, mainly in the mid- to upper-villus regions in which the brush-border membrane also stained strongly with GLUTS. Perfusion of glucose for 4 h had little effect on fructose or glucose uptake and PIP 3 or GLUTS staining. SH-5, an Akt inhibitor, prevented the increase in fructose uptake and GLUTS protein induced by fructose solutions, and had no effect on glucose uptake, The PI3-kinase/Akt signaling pathway may be involved in the synthesis and/or recruitment to the brush border of GLUTS transporters by luminal fructose in the small intestine of weaning rats. Increases in fructose transport during the critical weaning period when rats are shifting to a new diet may be modulated by several signaling pathways whose cross talk during development still needs to be elucidated.
|Original language||English (US)|
|Journal||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|Issue number||6 51-6|
|State||Published - Jun 2005|
All Science Journal Classification (ASJC) codes
- Physiology (medical)
- Epidermal growth factor