Recombinant insulin-like growth factor I normalizes expression of renal glucose transporters in diabetic rats.
By immunocytochemistry we have studied the effect of recombinant human insulin-like growth factor I (rhIGF-I) on expression of renal GLUT-1, -2, and -5 in rats with streptozotocin (STZ)-induced diabetes. In the renal tubules of these rats, expression of GLUT-1 was reduced and that of GLUT-2 was increased. GLUT-1 expression was restored, and GLUT-2 expression was normalized by 2-wk administration of rhIGF-I. We have shown that GLUT-5 was expressed at the brush-border membrane of the proximal convoluted tubules (PCT) of the cortex and at the glomerular mesangial cells (GMC) in normal rat kidney. In the diabetic rats, GLUT-5 expression was increased at both sites, along with an increase of GLUT-2 expression at the basolateral membrane of PCT, and was decreased to normal level at both sites by treatment with rhIGF-I. Thus, like GLUT-2, GLUT-5 is suggested to regulate glucose reabsorption in PCT. The relationship between overexpression of GLUT-5 in GMC and accumulation of sorbitol and advanced glycosylation end products are discussed. Regulation of GLUT expression may play an important role on renal glucose homeostasis.
Asada
T
T
Pharmacological Research Laboratories, Fujisawa Pharmaceutical, Osaka, Japan.
Ogawa
T
T
Iwai
M
M
Shimomura
K
K
Kobayashi
M
M
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects; D005920:Glomerular Mesangium / Q000378:metabolism; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007672:Kidney Cortex / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000378:metabolism; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis*; D009124:Muscle Proteins; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D015430:Weight Gain / Q000187:drug effects
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011994:Recombinant Proteins; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D007334:Insulin-Like Growth Factor I; D006003:Glycogen