The role of PI 3-kinase in EGF-stimulated jejunal glucose transport

Epidermal growth factor (EGF) rapidly increases jejunal glucose transport. Signal transduction mechanisms mediating EGF-induced alterations in jejunal glucose transport remain to be determined. New Zealand White rabbit (1 kg) jejunal tissue was stripped and mounted in short-circuited Ussing chambers. The transport of tritiated 3-O-methylglucose was measured in the presence of the PKC agonist 1,2-dioctanoyl-sn-glycerol (1,2-DOG) or the inactive analog 1,3-dioctanoyl-sn-glycerol (1,3-DOG). Additional experiments examined the effect of the PKC inhibitor chelerythrine, the PLC inhibitor U73122, the MAPK inhibitor PD 98059, the G-protein inhibitor GDP-βS, the PI 3-kinase inhibitor LY294002, or the microtubule inhibitor colchicine on EGF-induced jejunal glucose transport. Net jejunal 3-O-methylglucose absorption was significantly increased following specific activation of PKC. A PKC antagonist inhibited the EGF-induced increase in net 3-O-methylglucose transport, while PI 3-kinase inhibition completely blocked the EGF-induced transport increase. Inhibition of PLC, MAPK, G-proteins, and microtubules had no effect on EGF-stimulated increases in jejunal transport. We conclude that the effect of EGF on jejunal glucose transport is mediated at least in part by PKC and PI 3-kinase.Key words: glucose transport, epidermal growth factor, protein kinase C, PI 3-kinase.

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 tissues treated with orally administered insulin-like growth factor-I (IGF-I) were studied in 5-day-old colostrum-deprived piglets. Human recombinant IGF-I (3.5 mg · kg−1 · day−1) or control vehicle was given orogastrically for 4 days. Disaccharidase activity, fructose uptake, and Na+-glucose cotransporter SGLT-1 protein abundance were similar between groups. Oral IGF-I produced greater rates of enterocyte Na+-K+-ATPase activity with no significant differences in Na+-K+-ATPase abundance. Cellular mechanisms responsible for transport changes were studied in Ussing chambers. In control tissues, the presence of IGF-I in mucosal solutions increased basal short-circuit current ( I sc), potential difference, d-glucose-stimulated I sc, and Na+-K+-ATPase activity; these changes were abolished by preincubation of tissues with wortmannin, a phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor. The results suggest that the effect of IGF-I on jejunal ion and nutrient transport involves activation of PI 3-kinase and stimulation of Na+-K+-ATPase activity in enterocytes.

Effect of Intraluminal Hydrocortisone on Solute and Water Absorption in the Human Jejunum

1. To compare the effects of intravenous and intraluminal hydrocortisone on jejunal transport, the proximal jejunum was perfused with glucose (28 mmol/l) in saline in two groups of normal subjects. 2. In the first group of seven subjects, compared with the control period results there were no changes in sodium, water and glucose absorption during the intravenous administration of hydrocortisone. In contrast, intraluminal hydrocortisone (100 mg/l) increased sodium, water and glucose absorption by 169%, 223% and 81% respectively (P < 0.001 in each case) above the control values, when peripheral plasma cortisol levels were similar to those achieved with intravenous hydrocortisone. 3. In the second group of three subjects, intraluminal hydrocortisone (10 mg/l and 30 mg/l), followed by an intravenous infusion of hydrocortisone, had no effects on sodium, water and glucose absorption. 4. In a third group of six normal subjects perfused with fructose (28 mmol/l) in saline and bicarbonate (28 mmol/l) in saline intraluminal hydrocortisone (100 mg/l) had no effect on solute and water absorption. 5. These results suggest that intraluminal hydrocortisone stimulates glucose-coupled sodium transport by exerting a topical effect on the apical membrane of the jejunal mucosa.

Postnatal development of intestinal bile salt transport in the guinea pig

The postnatal development of intestinal bile salt transport was examined in the guinea pig. Using an in vitro technique, mucosal uptake of taurocholate was measured in jejunum and ileum at five monomeric concentrations from fetal, 1-day-old, 5-day-old, 10-day-old, 21-day-old, and adult animals. Jejunal taurocholate uptake was linear with respect to concentration and was not inhibited by taurochenodeoxycholate at all ages studied. In fetal and 1-day-old animals, ileal taurocholate uptake was linear and was not inhibited by taurochenodeoxycholate. A curvilinear relation between uptake and taurocholate concentration, which was inhibited by taurochenodeoxycholate, was observed in 5-day-old and older animals. These findings indicate that, in the guinea pig, passive diffusion of taurocholate is the only mode of intestinal transport in fetuses and newborns and the sole mode of jejunal transport at all ages. By 5 days, however, active ileal transport appears, which persists into adulthood and contributes to the development of an efficient enterohepatic circulation of bile salts.