Regulation of growth factor mRNA levels in the eyes of diabetic rats.
The underlying etiology of diabetic microvascular disease remains unknown. To examine the potential contribution of basic fibroblast growth factor (bFGF), which is an angiogenic factor, and insulin-like growth factor-I (IGF-I) to the development of diabetic microvascular disease, bFGF and IGF-I mRNA levels were measured in tissues of control, diabetic, and insulin-treated diabetic rats. Diabetes was induced in rats by intravenous injection of streptozotocin (STZ) 65 mg/kg, and the rats were maintained for 21 days. bFGF mRNA levels increased threefold in the eyes of diabetic versus control rats, whereas a consistent change in bFGF mRNA levels was not observed in other tissues. In contrast, IGF-I mRNA levels decreased in the eyes and other tissues, including kidney, lung, and skeletal muscle, of diabetic as compared with control rats. Insulin treatment prevented the diabetes-induced increase in bFGF and decrease in IGF-I mRNA levels. Acidic FGF (aFGF) mRNA levels were unchanged in eyes from diabetic versus control rats. In partially purified retinas, diabetes increased bFGF mRNA levels twofold as compared with levels in control retinas, whereas IGF-I mRNA levels decreased to 58% of control levels in retinas from diabetic rats. Insulin treatment again prevented the diabetes-induced increase in IGF-I mRNA levels in the retina but had no effect on the diabetes-induced increase in bFGF mRNA levels. bFGF peptide levels were minimally increased in diabetic versus control retinas.(ABSTRACT TRUNCATED AT 250 WORDS)
Lowe
W L
WL
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA.
Florkiewicz
R Z
RZ
Yorek
M A
MA
Spanheimer
R G
RG
Albrecht
B N
BN
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000209:etiology / Q000503:physiopathology; D005123:Eye / Q000737:chemistry* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D005632:Fructose / Q000032:analysis / Q000378:metabolism; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007294:Inositol / Q000032:analysis / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013012:Sorbitol / Q000494:pharmacology; D013311:Streptozocin
D007093:Imidazoles; D048289:Imidazolidines; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D005632:Fructose; D007294:Inositol; D013012:Sorbitol; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I; D000449:Aldehyde Reductase; C026411:sorbinil; D005947:Glucose