Differential Tissue Regulation of Insulinlike Growth Factor Binding Proteins in Experimental Diabetes Mellitus in the Rat Free

The expression and regulation of IGF-I is tissue-specific in diabetes mellitus in the rat. These studies were designed to examine if similar tissue specificity exists for IGF-BPs in the diabetic milieu. Diabetes mellitus was induced by a single i.p. injection of STZ (100 mg/kg body weight). Rats were treated with either vehicle—Insulin, vanadate, or phlorizin for 7–14 days. Tissues were analyzed for IGF-BPs by ligand blotting and by affinity cross-linking and immunoprecipitation. In liver tissue from nondiabetic control rats, multiple forms of IGF-BPs were noted, ranging from 48,000 to 25,000 M_r. In diabetic rat liver tissue, the 25,000-M_r form was unchanged, whereas the higher M_r forms (48,000–42,000 M_r) were decreased, and the 30,000-Afr form was increased. Insulin therapy of diabetic rats decreased all forms to below control levels. In the kidney tissue of control rats, faint IGF-BP bands were seen at 30,000 and 25,000 M_r In diabetic rat kidney tissue, the 30,000-Afr form again was increased (as in liver) and restored to control levels with insulin therapy. In contrast, only a 30,000-Afr band was seen in control pituitary tissue, which was slightly increased in the diabetic rats and also was decreased below control levels by insulin. In hypothalamus and cerebral cortex tissue, bands at 30,000 and 25,000 M_r were noted, and neither was altered by diabetes or insulin treatment. Treatment of diabetic rats with vanadate and phlorizin resulted in comparable blood glucose levels, which were only slightly higher than those achieved with insulin therapy. However, although tissue IGF-BPs from vanadate-treated rats were similar to those with insulin therapy, phlorizin was without effect. Immunoprecipitation demonstrated that IGF-BP-1 and IGF-BPs were increased in the livers and kidneys of diabetic animals (presumably represented by the 30,000-Afr band on ligand blotting). In pituitary, hypothalamus, and cerebral cortex tissue, IGF-BPs was the predominant species of BP identified. Although the diabetic state caused increases in BPs in pituitary, no changes were noted in the cerebral cortex and hypothalamus. Therefore, these data suggest that the IGF-BPs in peripheral and neural tissues are differentially regulated by insulin and glucose.