Serum somatomedin levels in adults with chronic renal failure: The importance of measuring insulin-like growth factor I (IGF-I) and IGF-II in acid-chromatographed uremic serum

D. R. Powell, Ronald (Ron) Rosenfeld, B. K. Baker, F. Liu, R. L. Hintz

Research output: Contribution to journalArticle

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Abstract

Somatomedin levels measured by radioreceptor assay (RRA) or RIA on acid-ethanol-extracted or unextracted serum from patients with uremia are quite variable relative to normal values. We have investigated whether compounds accumulating in uremic serum were interfering with these RRA and RIA measurements. Insulin-like growth factor I (IGF-I) and IGF-II were separated from carrier proteins by either Sephadex G-50 acid chromatography or acid-ethanol extraction. IGF-I was measured by RIA, and IGF-II was determined by rat placental membrane RRA. IGF-I levels in the acid-ethanol extracts of serum from eight uremic adults were only 50% of the levels found in seven normal subjects, and IGF-II levels in these uremic patients were 350% of normal values. However, these significant differences were not found when comparable serum samples were acid chromatographed rather than acid-ethanol extracted; instead, IGF-I levels were 343 ± 168 (mean ± SD) ng/ml in uremic patients and 325 ± 54 ng/ml in normal subjects, while IGF-II levels were 780 ± 215 ng/ml in uremic patients and 588 ± 46 ng/ml in normal subjects. To determine whether compounds that interfere with somatomedin assays were present in the acid-ethanol extracts of uremic serum, we acid chromatographed these extracts and found that a compound eluting in the carrier protein fraction of the uremic extract artifactually decreased IGF-I levels measured by RIA and increased IGF-II levels measured by RRA. We also found that unsaturated carrier protein binding of IGF-I and IGF-II was significantly increased in the carrier protein fraction of uremic acid-ethanol extracts at the dilutions used for somatomedin assays. We conclude that acid chromatography for unextracted or acid-ethanol-extracted uremic serum is necessary to remove a compound, probably unsaturated carrier protein, which interferes with RIA of IGF-I and RRA of IGF-II. Once this compound is removed, serum IGF-I levels (RIA) in uremic patients are not different from normal, and serum IGF-II levels (RRA) are not lower than normal.

Original languageEnglish (US)
Pages (from-to)1186-1192
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume63
Issue number5
StatePublished - 1986
Externally publishedYes

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Insulin-Like Growth Factor II
Somatomedins
Insulin-Like Growth Factor I
Chronic Kidney Failure
Radioligand Assay
Assays
Acids
Ethanol
Serum
Carrier Proteins
Chromatography
Reference Values
Unsaturated compounds
Uremia
Protein Binding
Dilution
Rats
Membranes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Serum somatomedin levels in adults with chronic renal failure : The importance of measuring insulin-like growth factor I (IGF-I) and IGF-II in acid-chromatographed uremic serum. / Powell, D. R.; Rosenfeld, Ronald (Ron); Baker, B. K.; Liu, F.; Hintz, R. L.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 63, No. 5, 1986, p. 1186-1192.

Research output: Contribution to journalArticle

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abstract = "Somatomedin levels measured by radioreceptor assay (RRA) or RIA on acid-ethanol-extracted or unextracted serum from patients with uremia are quite variable relative to normal values. We have investigated whether compounds accumulating in uremic serum were interfering with these RRA and RIA measurements. Insulin-like growth factor I (IGF-I) and IGF-II were separated from carrier proteins by either Sephadex G-50 acid chromatography or acid-ethanol extraction. IGF-I was measured by RIA, and IGF-II was determined by rat placental membrane RRA. IGF-I levels in the acid-ethanol extracts of serum from eight uremic adults were only 50{\%} of the levels found in seven normal subjects, and IGF-II levels in these uremic patients were 350{\%} of normal values. However, these significant differences were not found when comparable serum samples were acid chromatographed rather than acid-ethanol extracted; instead, IGF-I levels were 343 ± 168 (mean ± SD) ng/ml in uremic patients and 325 ± 54 ng/ml in normal subjects, while IGF-II levels were 780 ± 215 ng/ml in uremic patients and 588 ± 46 ng/ml in normal subjects. To determine whether compounds that interfere with somatomedin assays were present in the acid-ethanol extracts of uremic serum, we acid chromatographed these extracts and found that a compound eluting in the carrier protein fraction of the uremic extract artifactually decreased IGF-I levels measured by RIA and increased IGF-II levels measured by RRA. We also found that unsaturated carrier protein binding of IGF-I and IGF-II was significantly increased in the carrier protein fraction of uremic acid-ethanol extracts at the dilutions used for somatomedin assays. We conclude that acid chromatography for unextracted or acid-ethanol-extracted uremic serum is necessary to remove a compound, probably unsaturated carrier protein, which interferes with RIA of IGF-I and RRA of IGF-II. Once this compound is removed, serum IGF-I levels (RIA) in uremic patients are not different from normal, and serum IGF-II levels (RRA) are not lower than normal.",
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T2 - The importance of measuring insulin-like growth factor I (IGF-I) and IGF-II in acid-chromatographed uremic serum

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AU - Rosenfeld, Ronald (Ron)

AU - Baker, B. K.

AU - Liu, F.

AU - Hintz, R. L.

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N2 - Somatomedin levels measured by radioreceptor assay (RRA) or RIA on acid-ethanol-extracted or unextracted serum from patients with uremia are quite variable relative to normal values. We have investigated whether compounds accumulating in uremic serum were interfering with these RRA and RIA measurements. Insulin-like growth factor I (IGF-I) and IGF-II were separated from carrier proteins by either Sephadex G-50 acid chromatography or acid-ethanol extraction. IGF-I was measured by RIA, and IGF-II was determined by rat placental membrane RRA. IGF-I levels in the acid-ethanol extracts of serum from eight uremic adults were only 50% of the levels found in seven normal subjects, and IGF-II levels in these uremic patients were 350% of normal values. However, these significant differences were not found when comparable serum samples were acid chromatographed rather than acid-ethanol extracted; instead, IGF-I levels were 343 ± 168 (mean ± SD) ng/ml in uremic patients and 325 ± 54 ng/ml in normal subjects, while IGF-II levels were 780 ± 215 ng/ml in uremic patients and 588 ± 46 ng/ml in normal subjects. To determine whether compounds that interfere with somatomedin assays were present in the acid-ethanol extracts of uremic serum, we acid chromatographed these extracts and found that a compound eluting in the carrier protein fraction of the uremic extract artifactually decreased IGF-I levels measured by RIA and increased IGF-II levels measured by RRA. We also found that unsaturated carrier protein binding of IGF-I and IGF-II was significantly increased in the carrier protein fraction of uremic acid-ethanol extracts at the dilutions used for somatomedin assays. We conclude that acid chromatography for unextracted or acid-ethanol-extracted uremic serum is necessary to remove a compound, probably unsaturated carrier protein, which interferes with RIA of IGF-I and RRA of IGF-II. Once this compound is removed, serum IGF-I levels (RIA) in uremic patients are not different from normal, and serum IGF-II levels (RRA) are not lower than normal.

AB - Somatomedin levels measured by radioreceptor assay (RRA) or RIA on acid-ethanol-extracted or unextracted serum from patients with uremia are quite variable relative to normal values. We have investigated whether compounds accumulating in uremic serum were interfering with these RRA and RIA measurements. Insulin-like growth factor I (IGF-I) and IGF-II were separated from carrier proteins by either Sephadex G-50 acid chromatography or acid-ethanol extraction. IGF-I was measured by RIA, and IGF-II was determined by rat placental membrane RRA. IGF-I levels in the acid-ethanol extracts of serum from eight uremic adults were only 50% of the levels found in seven normal subjects, and IGF-II levels in these uremic patients were 350% of normal values. However, these significant differences were not found when comparable serum samples were acid chromatographed rather than acid-ethanol extracted; instead, IGF-I levels were 343 ± 168 (mean ± SD) ng/ml in uremic patients and 325 ± 54 ng/ml in normal subjects, while IGF-II levels were 780 ± 215 ng/ml in uremic patients and 588 ± 46 ng/ml in normal subjects. To determine whether compounds that interfere with somatomedin assays were present in the acid-ethanol extracts of uremic serum, we acid chromatographed these extracts and found that a compound eluting in the carrier protein fraction of the uremic extract artifactually decreased IGF-I levels measured by RIA and increased IGF-II levels measured by RRA. We also found that unsaturated carrier protein binding of IGF-I and IGF-II was significantly increased in the carrier protein fraction of uremic acid-ethanol extracts at the dilutions used for somatomedin assays. We conclude that acid chromatography for unextracted or acid-ethanol-extracted uremic serum is necessary to remove a compound, probably unsaturated carrier protein, which interferes with RIA of IGF-I and RRA of IGF-II. Once this compound is removed, serum IGF-I levels (RIA) in uremic patients are not different from normal, and serum IGF-II levels (RRA) are not lower than normal.

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