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Basolateral D‐glucose transport activity along the crypt‐villus axis in rat jejunum and upregulation induced by gastric inhibitory peptide and glucagon‐like peptide−2
Author(s) -
Cheeseman CI,
O'Neill D
Publication year - 1998
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.1998.sp004142
Subject(s) - downregulation and upregulation , crypt , glucagon like peptide 1 , jejunum , endocrinology , medicine , gastric inhibitory polypeptide , chemistry , peptide , glucose transporter , inhibitory postsynaptic potential , glucagon , biology , biochemistry , insulin , diabetes mellitus , gene , type 2 diabetes
Phloridzin‐insensitive D‐glucose uptake into enterocytes isolated sequentially from along the crypt‐villus axis showed the majority of transport activity to reside in cells from the upper third of the villus. In contrast, total postnuclear glucose transporter 2 (GLUT2) protein content of the cells was high even close to the crypt and was almost constant for the upper 80% of the villi. A 4 h lumenal perfusion in vivo with 100 mM D‐glucose prior to harvesting the enterocytes produced a 2‐ to 3‐fold increase in phloridzin‐insensitive D‐glucose uptake which extended down 70% of the villus. Vascular infusion in vivo with either 800 pM gastric inhibitory polypeptide (GIP) or glucagon‐like peptide‐2 (GLP‐2) prior to harvesting enterocytes produced the same response as lumenal glucose, while glucagon like peptide‐1 (GLP‐1) had no effect. Inclusion of 30 microM brefeldin A (BFA), an inhibitor of protein trafficking, in the lumenal perfusate produced a small, but not significant, increase in the control uptake profile along the villus in isolated enterocytes. However, BFA significantly reduced the upregulation induced by lumenal glucose and vascular GIP and blocked the stimulation produced by vascular GLP‐2. Biotinylation of surface proteins and isolation with protein A indicated that there was no change in the membrane abundance of GLUT2 after GLP‐2 treatment. These results are discussed in relation to the role of gastrointestinal peptide hormones in controlling intestinal hexose transport and the possibility of protein trafficking being involved in mediating the upregulation of GLUT2 activity in the enterocyte basolateral membrane.