Experimental diabetes increases insulin-like growth factor I and II receptor concentration and gene expression in kidney

Journal Article · Sat Dec 01 00:00:00 EST 1990 · Diabetes; (USA)

DOI:https://doi.org/10.2337/diab.39.12.1490· OSTI ID:6321336

Werner, H; Shen-Orr, Z; Stannard, B; Burguera, B; Roberts, Jr, C T; LeRoith, D ^[1]

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1. National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (USA)

Insulinlike growth factor I (IGF-I) is a mitogenic hormone with important regulatory roles in growth and development. One of the target organs for IGF-I action is the kidney, which synthesizes abundant IGF-I receptors and IGF-I itself. To study the involvement of IGF-I and the IGF-I receptor in the development of nephropathy, one of the major complications of diabetes mellitus, we measured the expression of these genes in the kidney and in other tissues of the streptozocin-induced diabetic rat. The binding of 125I-labeled IGF-I to crude membranes was measured in the same tissues. We observed a 2.5-fold increase in the steady-state level of IGF-I-receptor mRNA in the diabetic kidney, which was accompanied by a 2.3-fold increase in IGF-I binding. In addition to this increase in IGF-I binding to the IGF-I receptor, there was also binding to a lower-molecular-weight material that may represent an IGF-binding protein. No change was detected in the level of IGF-I-peptide mRNA. Similarly, IGF-II-receptor mRNA levels and IGF-II binding were significantly increased in the diabetic kidney. IGF-I- and IGF-II-receptor mRNA levels and IGF-I and IGF-II binding returned to control values after insulin treatment. Because the IGF-I receptor is able to transduce mitogenic signals on activation of its tyrosine kinase domain, we hypothesize that, among other factors, high levels of receptor in the diabetic kidney may also be involved in the development of diabetic nephropathy. Increased IGF-II-receptor expression in the diabetic kidney may be important for the intracellular transport and packaging of lysosomal enzymes, although a role for this receptor in signal transduction cannot be excluded. Finally, the possible role of IGF-binding proteins requires further study.

• OSTI ID: 6321336
• Journal Information: Diabetes; (USA), Vol. 39:12; ISSN 0012-1797
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DIABETES MELLITUS
PATHOGENESIS
GROWTH FACTORS
RECEPTORS
KIDNEYS
GENE REGULATION
BIOCHEMICAL REACTION KINETICS
CELL MEMBRANES
INSULIN
IODINE 125
MESSENGER-RNA
MOLECULAR WEIGHT
PHOSPHOTRANSFERASES
TRACER TECHNIQUES
BETA DECAY RADIOISOTOPES
BODY
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE DISEASES
ENZYMES
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MEMBRANE PROTEINS
MEMBRANES
METABOLIC DISEASES
MITOGENS
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RNA
TRANSFERASES
550901* - Pathology- Tracer Techniques