Small intestine hexose transport in experimental diabetes. Increased transporter mRNA and protein expression in enterocytes.
The effect of insulinopenic diabetes on the expression of glucose transporters in the small intestine was investigated. Enterocytes were sequentially isolated from jejunum and ileum of normal fed rats, streptozotocin-diabetic rats, and diabetic rats treated with insulin. Facilitative glucose transporter (GLUT) 2, GLUT5, and sodium-dependent glucose transporter 1 protein content was increased from 1.5- to 6-fold in enterocytes isolated from diabetic animals in both jejunum and ileum. Insulin was able to reverse the increase in transporter protein expression seen after induction of diabetes. There was a four- to eightfold increase in the amount of enterocyte glucose transporter mRNA after diabetes with greater changes in sodium-dependent glucose transporter 1 and GLUT2 than in GLUT5 levels. In situ hybridization showed that after the induction of diabetes there was new hybridization in lower villus and crypt enterocytes that was reversed by insulin treatment. Thus, the increase in total hexose transport caused by diabetes is due to a premature expression of hexose transporters by enterocytes along the crypt-villus axis, causing a cumulative increase in enterocyte transporter protein during maturation. These changes are likely to represent an adaptive response by the organism to increase nutrient absorption in a perceived state of tissue starvation. These adaptive changes may lead to exacerbation of hyperglycemia in uncontrolled diabetes.
Burant
C F
CF
Department of Medicine, University of Chicago, Illinois 60637.
Flink
S
S
DePaoli
A M
AM
Chen
J
J
Lee
W S
WS
Hediger
M A
MA
Buse
J B
JB
Chang
E B
EB
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D007082:Ileum / Q000378:metabolism*; D017403:In Situ Hybridization; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat