Alterations of glucose transporter systems in insulin-resistant uremic rats.
To further define the cellular alteration(s) involved in the impaired glucose transport associated with chronic uremia, we examined the concentration and translocation of glucose transport systems in adipocytes isolated from partially nephrectomized uremic rats. Uremic animals, compared with matched controls, had increased blood urea nitrogen and serum insulin, whereas serum glucose was unchanged. In agreement with previous work, 125I-insulin binding to its receptor was unaltered and transport of 2-deoxy-D-glucose was decreased in both the absence (basal) and presence of a maximal (7 nM) insulin concentration by 44 and 35%, respectively. To assess the movement and concentration of glucose transport systems in various membrane fractions prepared from basal and insulin-treated (20 nM) uremic fat cells, the technique of D-glucose-inhibitable cytochalasin B binding was utilized. In plasma membranes isolated from these cells the concentration of glucose transporters was decreased by 16 (P less than 0.01) and 30% (P less than 0.005) in basal and insulin-treated cells, respectively. Concomitantly, microsomal membranes prepared from uremic cells treated in the absence and presence of insulin had a 28 (P less than 0.01) and 15% (P less than 0.05) decrease in concentration of glucose transport systems, respectively. Additionally, glucose transporter concentration was significantly decreased by 17% (P less than 0.025) in total membranes prepared from uremic cells. Thus, impairment of glucose transport in uremic fat cells can be attributed to a postbinding defect that, at least in part, results from a decrease in the total concentration of glucose transporters.(ABSTRACT TRUNCATED AT 250 WORDS)
Jacobs
D B
DB
Department of Medicine, University of Rochester School of Medicine, New York 14642.
Hayes
G R
GR
Truglia
J A
JA
Lockwood
D H
DH
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism; D012016:Reference Values; D014511:Uremia / Q000378:metabolism*
D007328:Insulin; D009004:Monosaccharide Transport Proteins; D003571:Cytochalasin B; D011972:Receptor, Insulin; D005947:Glucose