Stress and glucocorticoid inhibit apical GLUT2-trafficking and intestinal glucose absorption in rat small intestine.
We have proposed a new model of rat intestinal sugar absorption in which high glucose concentrations promote rapid insertion of GLUT2 into the apical membrane, so that absorptive capacity is precisely regulated to match dietary intake. Construction and building work during expansion and refurbishment of our department permitted opportunistic experiments on the effects of building-induced stress on the GLUT2 component of absorption. In fed rats perfused with 75 mM glucose in vivo, stress rapidly inhibited glucose absorption 36.4 +/- 3.0% compared with control rats. Selective inhibition of the GLUT2 component with phloretin demonstrated that stress inhibited the GLUT2 component by 42.8 +/- 3.8%, which correlated with a corresponding diminution in apical GLUT2 levels: the SGLT1 component and its level were unaltered by stress. Effects of stress were reversed by the administration in drinking water of metyrapone, which inhibits 11-beta-hydroxylase. Injection of dexamethasone into control rats 60 min before perfusion resulted in absorption and transporter properties indistinguishable from stressed rats. Our data are consistent with the view that stress activates the hypothalamus-pituitary-adrenal (HPA) axis, causing release of glucocorticoid. The ensuing inhibition of GLUT2 trafficking and absorption seems necessary to prevent enhanced intestinal delivery of glucose to the circulation from antagonizing the essential stress response of glucorticoid in mobilizing peripheral energy stores for emergency purposes.
Shepherd
Emma J
EJ
Department of Biology, University of York, York YO10 5YW, UK. ejs9@york.ac.uk.
Helliwell
Philip A
PA
Mace
Oliver J
OJ
Morgan
Emma L
EL
Patel
Nick
N
Kellett
George L
GL
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005160:Facility Design and Construction; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000493:pharmacokinetics*; D051273:Glucose Transporter Type 2; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009622:Noise; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D003907:Dexamethasone; D005947:Glucose; D008797:Metyrapone