Involvement of PI 3-kinase in IGF-I stimulation of jejunal Na+-K+-ATPase activity and nutrient absorption

Mechanisms responsible for increased jejunal transport rates observed in ti ssues treated with orally administered insulin-like growth factor-I (IGF-I) were studied in 5-day-old colostrum-deprived piglets. Human recombinant IG F-I (3.5 mg.kg(-1).day(-1)) or control vehicle was given orogastrically for 4 days. Disaccharidase activity, fructose uptake, and Na+-glucose cotransp orter SGLT-1 protein abundance were similar between groups. Oral IGF-I prod uced greater rates of enterocyte Na+-K+-ATPase activity with no significant differences in Na+-K+-ATPase abundance. Cellular mechanisms responsible fo r transport changes were studied in Ussing chambers. In control tissues, th e presence of IGF-I in mucosal solutions increased basal short-circuit curr ent (I-sc), potential difference, D-glucose-stimulated I-sc, and Na+-K+-ATP ase activity; these changes were abolished by preincubation of tissues with wortmannin, a phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor. The r esults suggest that the effect of IGF-I on jejunal ion and nutrient transpo rt involves activation of PI 3-kinase and stimulation of Na+-K+-ATPase acti vity in enterocytes.