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

• Published in: Canadian journal of physiology and pharmacology 2002-01, Vol.80 (1), p.77-84
• Main Authors: Millar, Grant A, Hardin, James A, Johnson, Leonard R, Gall, D Grant
• Format: Article
• Language: English
• Subjects: 3-O-Methylglucose - metabolism; Animals; Biological and medical sciences; Biological Transport, Active - drug effects; Diffusion Chambers, Culture; Enzymes; Epidermal Growth Factor - pharmacology; Fundamental and applied biological sciences. Psychology; Gastrointestinal tract; Glucose; Glucose - metabolism; In Vitro Techniques; Intestine. Mesentery; Jejunum - drug effects; Jejunum - enzymology; Jejunum - metabolism; Kinetics; Microvilli - drug effects; Microvilli - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Rabbits; rho GTP-Binding Proteins - metabolism; Signal Transduction - drug effects; Stimulation, Chemical; Subcellular Fractions - drug effects; Subcellular Fractions - metabolism; Vertebrates: digestive system
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y02-012

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.