Altered renal expression of the insulin-responsive glucose transporter GLUT4 in experimental diabetes mellitus.
Because the insulin-responsive glucose transporter, GLUT4, is expressed in renal vascular and glomerular cells, we determined the effects of experimental diabetes mellitus on GLUT4 expression and glucose uptake by these tissues. Quantitative reverse-transcription polymerase chain reaction studies of microdissected afferent microvessels and renal glomeruli showed that, after 1 wk of diabetes, GLUT4 mRNA was decreased to 26 and 34% of control values, respectively. GLUT4 immunoblots of renal glomerular and microvessel samples showed that GLUT4 polypeptide was decreased to 51% of control values. These results were confirmed by indirect immunofluorescence, which showed decreased GLUT4 expression in glomerular cells and in vascular smooth muscle cells of the afferent microvasculature of diabetic animals. Uptake of the glucose analogue, 2-deoxyglucose, was also depressed in microvessels of diabetic rats to 57% of control values, supporting the conclusion that fewer total glucose transporters were available for glucose uptake into diabetic renal glomerular and microvascular cells. Thus both GLUT4 expression and glucose uptake by glomerular and microvascular cells are decreased in diabetic animals. These results have led us to suggest a mechanism by which decreased renal GLUT4 expression could contribute to glomerular hyperfiltration and hypertension seen in early diabetes.
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0676.
R G
RG
Marcus
R
R
England
K
K
Nguyen
M J
MJ
Charron
J P
JP
Briggs
F C
FC
Brosius
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D017931:DNA Primers; D003847:Deoxyglucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D051275:Glucose Transporter Type 4; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000378:metabolism*; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects; D009124:Muscle Proteins; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012077:Renal Artery / Q000378:metabolism*; D012079:Renal Circulation
D017931:DNA Primers; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D003847:Deoxyglucose