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Title: Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors

Abstract

The authors reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated big IGF-II. They now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Sephadex G-200. Normally about 75% of IGFs are carried as a ternary complex of 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching themore » target cells would result.« less

Authors:
;  [1]
  1. (Washington Univ. School of Medicine, St. Louis, MO (USA))
Publication Date:
OSTI Identifier:
7067287
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA); Journal Volume: 86:17
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; GROWTH FACTORS; CROSS-LINKING; METABOLIC DISEASES; PATHOGENESIS; PANCREAS; NEOPLASMS; BLOOD SERUM; GENES; INSULIN; IODINE 125; PATIENTS; RECOMBINANT DNA; SARCOMAS; BETA DECAY RADIOISOTOPES; BODY; CHEMICAL REACTIONS; DAYS LIVING RADIOISOTOPES; DIGESTIVE SYSTEM; DISEASES; DNA; ELECTRON CAPTURE RADIOISOTOPES; ENDOCRINE GLANDS; GLANDS; HORMONES; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPES; MITOGENS; NUCLEI; NUCLEIC ACIDS; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; PEPTIDE HORMONES; POLYMERIZATION; PROTEINS; RADIOISOTOPES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Daughaday, W.H., and Kapadia, M.. Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors. United States: N. p., 1989. Web. doi:10.1073/pnas.86.17.6778.
Daughaday, W.H., & Kapadia, M.. Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors. United States. doi:10.1073/pnas.86.17.6778.
Daughaday, W.H., and Kapadia, M.. Fri . "Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors". United States. doi:10.1073/pnas.86.17.6778.
@article{osti_7067287,
title = {Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors},
author = {Daughaday, W.H. and Kapadia, M.},
abstractNote = {The authors reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated big IGF-II. They now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Sephadex G-200. Normally about 75% of IGFs are carried as a ternary complex of 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching the target cells would result.},
doi = {10.1073/pnas.86.17.6778},
journal = {Proceedings of the National Academy of Sciences of the United States of America; (USA)},
number = ,
volume = 86:17,
place = {United States},
year = {Fri Sep 01 00:00:00 EDT 1989},
month = {Fri Sep 01 00:00:00 EDT 1989}
}