The effects of streptozotocin diabetes on sodium-glucose transporter (SGLT1) expression and function in rat jejunal and ileal villus-attached enterocytes.
Rats treated with streptozotocin for 17 days were used to determine the cellular origin of enhanced brush border glucose transport in the diabetic small intestine. In the jejunum of both normal and diabetic rats, phlorizin-sensitive (SGLT1-mediated) glucose transport was shown, by section autoradiography, to take place in upper villus enterocytes. The distribution of brush border SGLT1 transporters along villi, determined using immunogold cytochemistry, was similar to that found for glucose uptake. Longer villi, supporting a larger number of absorbing enterocytes in the diabetic jejunum, appeared to be responsible for increased glucose uptake in this condition. SGLT1 protein and SGLT1-mediated glucose transport were undetectable in normal distal ileal villi. However, following treatment with streptozotocin, both SGLT1 protein and SGLT1-mediated glucose transport were found to be present in basal ileal villus enterocytes. SGLT1 protein and SGLT1-mediated glucose transport both increased during enterocyte migration to the villus tip. Cellular induction of the SGLT1 transporter, as well as longer villi contribute to enhanced glucose transport in diabetic rat distal ileum. Close correlation between the positional expression of SGLT1 protein and absorptive function suggests that transporter density is an important determinant for up-regulation of sodium-dependent glucose transport in diabetes.
Debnam
E S
ES
Department of Physiology, Royal Free Hospital School of Medicine, London, UK.
Smith
M W
MW
Sharp
P A
PA
Srai
S K
SK
Turvey
A
A
Keable
S J
SJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007082:Ileum / Q000737:chemistry / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007583:Jejunum / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D008871:Microvilli / Q000737:chemistry; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D012964:Sodium; D010695:Phlorhizin; D005947:Glucose