Diabetes, Vol 41, Issue 4 499-507, Copyright © 1992 by American Diabetes Association

ARTICLES

Focal induction of IGF binding proteins in proximal tubules of diabetic rat kidney

LA Bach, AJ Cox, FA Mendelsohn, AC Herington, GA Werther and G Jerums
Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.

Diabetes-associated kidney enlargement is associated with increased kidney insulinlike growth factor I (IGF-I) binding. IGF-I binds to the type I IGF receptor, which mediates most of its actions, and to specific binding proteins (IGFBPs), which modulate its actions. To explore the nature and extent of IGF-I binding in the kidney, in vitro autoradiography was used to map the distribution of IGF binding in control and diabetic rat kidney. Specificity studies were performed with increasing concentrations of unlabeled IGF-I, IGF-II, des(1-3)IGF-I (an IGF-I derivative that binds to receptors normally but with decreased affinity to binding proteins), and insulin. In control rats, diffuse binding was found throughout the kidney with increased density in the papilla. Binding specificity in the cortex and outer medulla was typical of the type I IGF receptor (IGF-I = des[1-3]IGF-I greater than IGF-II much greater than insulin). Binding in the outer medulla of diabetic kidney was typical of the type I IGF receptor. A marked focal increase in proximal tubular binding occurred in 13 of 22 postpubertal diabetic rats. Binding specificity of the proximal tubular binding was consistent with the predominance of an IGF binding protein (IGF-I = IGF-II greater than des[1-3]IGF-I with minimal displacement by insulin). Northern-blot analysis revealed increased IGFBP-1 and IGFBP-3 mRNA in cortical tissue from diabetic rats displaying increased proximal tubular binding but not from diabetic rats not displaying this phenomenon. As cell surface association of IGFBPs is linked to potentiation of IGF activity, a possible mechanism for potentiation of local IGF-I action may be provided.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. De la Puente, L. Goya, S. Ramos, M. A. Martin, C. Alvarez, F. Escriva, and A. M. Pascual-Leone Effects of experimental diabetes on renal IGF/IGFBP system during neonatal period in the rat Am J Physiol Renal Physiol, December 1, 2000; 279(6): F1067 - F1076. [Abstract] [Full Text] [PDF]

				L. A. Bach, R. Dean, S. Youssef, and M. E. Cooper Aminoguanidine ameliorates changes in the IGF system in experimental diabetic nephropathy Nephrol. Dial. Transplant., March 1, 2000; 15(3): 347 - 354. [Abstract] [Full Text] [PDF]

				M. Shinada, A. Akdeniz, S. Panagiotopoulos, G. Jerums, and L. A. Bach Proteolysis of Insulin-Like Growth Factor-Binding Protein-3 Is Increased in Urine from Patients with Diabetic Nephropathy J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1163 - 1169. [Abstract] [Full Text]

				M. Karas, M. Danilenko, D. Fishman, D. LeRoith, J. Levy, and Y. Sharoni Membrane-associated Insulin-like Growth Factor-binding Protein-3 Inhibits Insulin-like Growth Factor-I-induced Insulin-like Growth Factor-I Receptor Signaling in Ishikawa Endometrial Cancer Cells J. Biol. Chem., June 27, 1997; 272(26): 16514 - 16520. [Abstract] [Full Text] [PDF]