Differential expression of the insulin-like growth factor binding proteins in spontaneously diabetic rats.
Diabetes-induced growth retardation in the rodent is associated with both reduced circulating insulin-like growth factor-I (IGF-I) and enhanced levels of inhibitors of somatomedin activity. IGF-binding proteins (IGFBPs) are present in the circulation and tissue fluids and are believed to modulate the actions of IGF-I. Since elevated concentrations of the IGFBPs may contribute to the enhanced somatomedin-inhibitor activity observed in serum from diabetic animals, we have examined the amounts of hepatic IGFBP-1, -2, -3 and -4 mRNA in the spontaneously diabetic BioBreeding/Worcester rat. The study used two types of diabetic animal: mildly diabetic animals, which received suboptimal insulin treatment (0.5-1 U/day) and diabetic animals, which received intensive insulin treatment (3-6 U/day). A significant increase in the amount of IGFBP-1 and IGFBP-2 mRNA was seen 1 month and 3 months after the onset of diabetes. Intensive insulin treatment for 3 weeks normalized the amount of IGFBP-1 mRNA in diabetic rats and resulted in a decrease in IGFBP-2 mRNA. In contrast to the increase in IGFBP-1 and IGFBP-2 mRNA, a significant decrease in IGFBP-3 mRNA was seen in diabetic rats (54.6% of control, P less than 0.0005 and 64.6% of control, P less than 0.005 for 1 and 3 months respectively) and intensive insulin treatment for 3 weeks did not restore the IGFBP-3 mRNA level in diabetic rats. No significant difference in IGFBP-4 mRNA levels was seen in diabetic compared with non-diabetic rats. When serum was analysed by ligand blotting the major finding was a reduction in the 39-42 kDa binding protein. No increase in 29-30 kDa IGFBP in the serum was detected in the diabetic rats. From these studies we conclude that the major change in IGFBPs in mildly hyperglycaemic spontaneously diabetic rats is a decrease in IGFBP-3. The changes in hepatic IGFBP-1 and -2 mRNA do not appear to be of sufficient magnitude to result in an increase in serum concentrations of these binding proteins.
Luo
J
J
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Murphy
L J
LJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006031:Glycosylation; D006454:Hemoglobins / Q000378:metabolism; D015151:Immunoblotting; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000302:isolation & purification; D051381:Rats; D011913:Rats, Inbred BB
D001786:Blood Glucose; D002352:Carrier Proteins; D006454:Hemoglobins; D018969:Insulin-Like Growth Factor Binding Proteins; D012313:RNA; D007334:Insulin-Like Growth Factor I