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-betaS, 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.
Millar
Grant A
GA
Gastrointestinal Research Group, Health Sciences Centre, University of Calgary, AB, Canada.
Hardin
James A
JA
Johnson
Leonard R
LR
Gall
D Grant
DG
D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D015194:Diffusion Chambers, Culture; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D019325:3-O-Methylglucose; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D020741:rho GTP-Binding Proteins; D005947:Glucose