Insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the kidney of the chronically hypoinsulinemic rat and hyperinsulinemic rat.
Acute streptozotocin (STZ)-induced diabetes in rats causes a transient increase in insulin-like growth factor-I (IGF-I) in the kidney, followed by a rapid renal hypertrophy and constant renal hyperperfusion. However, renal IGF-I levels return to normal within 4 days. Thus, hyperperfusion, which is independent of renal hypertrophy of the chronically diabetic kidney, is not explained by increased renal IGF-I. We studied IGF-I and IGF-I receptor gene expression in the kidney of rats with long-standing STZ-induced diabetes. IGF-I mRNA level in the chronically diabetic kidney was approximately 50% of that in control rats, whereas IGF-I receptor mRNA was increased approximately threefold. Ten days' treatment with insulin 65 days after induction of diabetes resulted in a glucose-dependent decrease in IGF-I receptor mRNA. Chronic hyperinsulinemia with near normoglycemia did not change gene expression of either IGF-I or IGF-I receptor. The studies suggest that glucose levels per se, independent of insulin levels, play an important role in the regulation of IGF-I receptor gene expression in the chronically diabetic kidney. Furthermore, kidney hyperperfusion in chronic diabetes is coupled with the increase in IGF-I receptor mRNA, despite normal kidney IGF-I levels.
Weiss
O
O
Department of Internal Medicine, Hadassah Ein Karem, Jerusalem, Israel.
Anner
H
H
Nephesh
I
I
Alayoff
A
A
Bursztyn
M
M
Raz
I
I
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D003720:Densitometry; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006946:Hyperinsulinism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006984:Hypertrophy; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D013311:Streptozocin; D013997:Time Factors
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1