Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney

Haim Werner, Zila Shen-Orr, Bethel Stannard, Bartolome Burguera, Charles Roberts, Derek Leroith

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1490-1497
Number of pages8
JournalDiabetes
Volume39
Issue number12
StatePublished - Dec 1990
Externally publishedYes

Fingerprint

Intercellular Signaling Peptides and Proteins
Kidney
Gene Expression
Growth Factor Receptors
IGF Type 2 Receptor
Insulin-Like Growth Factor Binding Proteins
Messenger RNA
Insulin-Like Growth Factor II
Diabetic Nephropathies
Product Packaging
Diabetes Complications
Streptozocin
Growth and Development
Protein-Tyrosine Kinases
Signal Transduction
Molecular Weight
Hormones
Insulin
Peptides
Membranes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Werner, H., Shen-Orr, Z., Stannard, B., Burguera, B., Roberts, C., & Leroith, D. (1990). Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney. Diabetes, 39(12), 1490-1497.

Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney. / Werner, Haim; Shen-Orr, Zila; Stannard, Bethel; Burguera, Bartolome; Roberts, Charles; Leroith, Derek.

In: Diabetes, Vol. 39, No. 12, 12.1990, p. 1490-1497.

Research output: Contribution to journalArticle

Werner, H, Shen-Orr, Z, Stannard, B, Burguera, B, Roberts, C & Leroith, D 1990, 'Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney', Diabetes, vol. 39, no. 12, pp. 1490-1497.
Werner, Haim ; Shen-Orr, Zila ; Stannard, Bethel ; Burguera, Bartolome ; Roberts, Charles ; Leroith, Derek. / Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney. In: Diabetes. 1990 ; Vol. 39, No. 12. pp. 1490-1497.
@article{ed4f0a4f574d4e4394bbcf738ba61c6e,
title = "Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney",
abstract = "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.",
author = "Haim Werner and Zila Shen-Orr and Bethel Stannard and Bartolome Burguera and Charles Roberts and Derek Leroith",
year = "1990",
month = "12",
language = "English (US)",
volume = "39",
pages = "1490--1497",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "12",

}

TY - JOUR

T1 - Experimental diabetes increases insulinlike growth factor I and II receptor concentration and gene expression in kidney

AU - Werner, Haim

AU - Shen-Orr, Zila

AU - Stannard, Bethel

AU - Burguera, Bartolome

AU - Roberts, Charles

AU - Leroith, Derek

PY - 1990/12

Y1 - 1990/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0025604999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025604999&partnerID=8YFLogxK

M3 - Article

C2 - 2174008

AN - SCOPUS:0025604999

VL - 39

SP - 1490

EP - 1497

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 12

ER -