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Stress and glucocorticoid inhibit apical GLUT2‐trafficking and intestinal glucose absorption in rat small intestine
Author(s) -
Shepherd Emma J.,
Helliwell Philip A.,
Mace Oliver J.,
Morgan Emma L.,
Patel Nick,
Kellett George L.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.072447
Subject(s) - glut2 , endocrinology , chemistry , medicine , absorption (acoustics) , glucose transporter , glucocorticoid , metyrapone , small intestine , biology , insulin , materials science , composite material
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 m m 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‐β‐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.