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 > IGF-II > > 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 > 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.
Skip Nav Destination
Article navigation
Original Articles|
April 01 1992
Focal Induction of IGF Binding Proteins in Proximal Tubules of Diabetic Rat Kidney
Leon A Bach;
Leon A Bach
Endocrine Unit, Department of Medicine, Austin Hospital
Heidelberg, Victoria
Departments of Biochemistry and Endocrinology, Royal Children's Hospital
Parkville, Victoria, Australia
Search for other works by this author on:
Alison J Cox;
Alison J Cox
Endocrine Unit, Department of Medicine, Austin Hospital
Heidelberg, Victoria
Departments of Biochemistry and Endocrinology, Royal Children's Hospital
Parkville, Victoria, Australia
Search for other works by this author on:
Frederick A O Mendelsohn;
Frederick A O Mendelsohn
Endocrine Unit, Department of Medicine, Austin Hospital
Heidelberg, Victoria
Departments of Biochemistry and Endocrinology, Royal Children's Hospital
Parkville, Victoria, Australia
Search for other works by this author on:
Adrian C Herington;
Adrian C Herington
Endocrine Unit, Department of Medicine, Austin Hospital
Heidelberg, Victoria
Departments of Biochemistry and Endocrinology, Royal Children's Hospital
Parkville, Victoria, Australia
Search for other works by this author on:
George A Werther;
George A Werther
Endocrine Unit, Department of Medicine, Austin Hospital
Heidelberg, Victoria
Departments of Biochemistry and Endocrinology, Royal Children's Hospital
Parkville, Victoria, Australia
Search for other works by this author on:
George Jerums
George Jerums
Endocrine Unit, Department of Medicine, Austin Hospital
Heidelberg, Victoria
Departments of Biochemistry and Endocrinology, Royal Children's Hospital
Parkville, Victoria, Australia
Search for other works by this author on:
Address correspondence and reprint requests to Dr. Leon Bach, NIDDK, NIH, Bldg 10, Rm 8D14, Bethesda, MD 20892.
Diabetes 1992;41(4):499–507
Article history
Received:
March 03 1991
Revision Received:
December 26 1991
Accepted:
December 26 1991
PubMed:
1376703
Citation
Leon A Bach, Alison J Cox, Frederick A O Mendelsohn, Adrian C Herington, George A Werther, George Jerums; Focal Induction of IGF Binding Proteins in Proximal Tubules of Diabetic Rat Kidney. Diabetes 1 April 1992; 41 (4): 499–507. https://doi.org/10.2337/diab.41.4.499
Download citation file:
9
Views