Journal of Clinical Endocrinology & Metabolism, Vol 67, 1225-1230, Copyright © 1988 by Endocrine Society

ARTICLES

Radioimmunoassay of a 26,000-dalton plasma insulin-like growth factor- binding protein: control by nutritional variables

WH Busby, DK Snyder and DR Clemmons
Department of Medicine, University of North Carolina, Chapel Hill 27599.

Insulin-like growth factor I (IGF-I) is a peptide growth factor that circulates bound to carrier proteins. One form of carrier protein (mol wt, approximately 26K) is not believed to be GH dependent, is relatively unsaturated, and modulates the cellular response to IGF-I. This study was undertaken to determine the variables that control the plasma concentration of this protein, which was measured using a specific RIA. The mean plasma 26K IGF-binding protein (IGF-BP) concentration in 15 normal fasting subjects at 0800 h was 9.4 +/- 4.4 (+/- SD) micrograms/L. The mean value in GH-deficient patients was increased to 19.5 +/- 10.1 micrograms/L (n = 60; P less than 0.05), and it was 7.3 +/- 4.3 micrograms/L in patients with acromegaly (n = 31). The GH dependency of these changes is further supported by the observation that subjects who received GH injections had a 51% reduction in their fasting values. Nutritional intake appeared to be a more important controlling variable than GH. During an overnight fast plasma 26K IGF-BP values increased approximately 4-fold in 6 normal subjects. After 2 days of fasting, the mean value in 7 obese subjects rose progressively from 6.5 +/- 2.3 to 11.7 +/- 5.4 micrograms/L (P less than 0.001), and it increased further to 19.2 +/- 5.9 micrograms/L by day 4 of fasting; after 2 days of refeeding it returned to the prefasting level of 6.8 +/- 1.9 micrograms/L. Likewise, ingestion of a standard test meal resulted in a significant decrease in mean plasma 26K IGF-BP from a fasting value of 8.4 +/- 2.9 to 5.6 +/- 2.8 micrograms/L 4 h postprandially (P less than 0.05). In summary, the plasma concentrations of the 26K IGF-I-BP fluctuate widely in response to dietary manipulation, whereas GH status appears to be a secondary controlling variable.

This article has been cited by other articles:

				M. Shimizu, B. R Beckman, A. Hara, and W. W Dickhoff Measurement of circulating salmon IGF binding protein-1: assay development, response to feeding ration and temperature, and relation to growth parameters J. Endocrinol., January 1, 2006; 188(1): 101 - 110. [Abstract] [Full Text] [PDF]

				V. Cingel-Ristic, J. W. van Neck, J. Frystyk, S. L. S. Drop, and A. Flyvbjerg Administration of Human Insulin-Like Growth Factor-Binding Protein-1 Increases Circulating Levels of Growth Hormone in Mice Endocrinology, September 1, 2004; 145(9): 4401 - 4407. [Abstract] [Full Text] [PDF]

				E. Giovannucci, E. B. Rimm, Y. Liu, M. Leitzmann, K. Wu, M. J. Stampfer, and W. C. Willett Body Mass Index and Risk of Prostate Cancer in U.S. Health Professionals J Natl Cancer Inst, August 20, 2003; 95(16): 1240 - 1244. [Abstract] [Full Text] [PDF]

				L. E. L. Katz, D. D. DeLeon, H. Zhao, and A. F. Jawad Free and Total Insulin-Like Growth Factor (IGF)-I Levels Decline during Fasting: Relationships with Insulin and IGF-Binding Protein-1 J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2978 - 2983. [Abstract] [Full Text] [PDF]

				K. Sakai, H. B. Lowman, and D. R. Clemmons Increases in Free, Unbound Insulin-like Growth Factor I Enhance Insulin Responsiveness in Human Hepatoma G2 Cells in Culture J. Biol. Chem., April 12, 2002; 277(16): 13620 - 13627. [Abstract] [Full Text] [PDF]

				D. R. Clemmons Use of Mutagenesis to Probe IGF-Binding Protein Structure/Function Relationships Endocr. Rev., December 1, 2001; 22(6): 800 - 817. [Abstract] [Full Text] [PDF]

				E. Giovannucci Insulin, Insulin-Like Growth Factors and Colon Cancer: A Review of the Evidence J. Nutr., November 1, 2001; 131(11): 3109S - 3120. [Abstract] [Full Text] [PDF]

				K. Sakai, A. J. D'Ercole, L. J. Murphy, and D. R. Clemmons Physiological Differences in Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Phosphorylation in IGFBP-1 Transgenic Mice Diabetes, January 1, 2001; 50(1): 32 - 38. [Abstract] [Full Text]

				A. Takenaka, N. Oki, S.-I. Takahashi, and T. Noguchi Dietary Restriction of Single Essential Amino Acids Reduces Plasma Insulin-Like Growth Factor-I (IGF-I) but Does Not Affect Plasma IGF-Binding Protein-1 in Rats J. Nutr., December 1, 2000; 130(12): 2910 - 2914. [Abstract] [Full Text] [PDF]

				E. Giovannucci, M. N. Pollak, E. A. Platz, W. C. Willett, M. J. Stampfer, N. Majeed, G. A. Colditz, F. E. Speizer, and S. E. Hankinson A Prospective Study of Plasma Insulin-like Growth Factor-1 and Binding Protein-3 and Risk of Colorectal Neoplasia in Women Cancer Epidemiol. Biomarkers Prev., April 1, 2000; 9(4): 345 - 349. [Abstract] [Full Text]

				A. Maxwell, R. Butterwick, R. M. Batt, and C. Camacho-Hübner Serum Insulin-Like Growth Factor (IGF)-I Concentrations Are Reduced by Short-Term Dietary Restriction and Restored by Refeeding in Domestic Cats (Felis catus) J. Nutr., October 1, 1999; 129(10): 1879 - 1884. [Abstract] [Full Text]

				R. C. Baxter Comment--Do Glucocorticoids Mediate the Hypoglycemia-Induced Rise in Insulin-Like Growth Factor Binding Protein-1? J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2259 - 2261. [Full Text]

				L. E. Levitt Katz, M. S. Satin-Smith, P. Collett-Solberg, L. Baker, C. A. Stanley, and P. Cohen Dual Regulation of Insulin-Like Growth Factor Binding Protein-1 Levels by Insulin and Cortisol during Fasting J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4426 - 4430. [Abstract] [Full Text]

				A. Barreca, M. Bozzola, A. Cesarone, P. H. Steenbergh, P. E. Holthuizen, F. Severi, G. Giordano, and F. Minuto Short Stature Associated with High Circulating Insulin-Like Growth Factor (IGF)-Binding Protein-1 and Low Circulating IGF-II: Effect of Growth Hormone Therapy J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3534 - 3541. [Abstract] [Full Text]

				S. Rajaram, D. J. Baylink, and S. Mohan Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions Endocr. Rev., December 1, 1997; 18(6): 801 - 831. [Abstract] [Full Text]

				J. Frystyk, T. Grofte, C. Skjarbak, and H. Orskov The Effect of Oral Glucose on Serum Free Insulin-Like Growth Factor-I and -II in Healthy Adults J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 3124 - 3127. [Abstract] [Full Text] [PDF]

				T. J. Nam, W. Busby Jr., D. R. Clemmons, T. J. Nam, W. Busby Jr., and D. R. Clemmons Insulin-Like Growth Factor Binding Protein-5 Binds to Plasminogen Activator Inhibitor-I Endocrinology, July 1, 1997; 138(7): 2972 - 2983. [Abstract] [Full Text] [PDF]

				L. Savendahl and L. E. Underwood Decreased Interleukin-2 Production from Cultured Peripheral Blood Mononuclear Cells in Human Acute Starvation J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1177 - 1180. [Abstract] [Full Text] [PDF]

				J. G. Reeve, A. Guadaņo, J. Xiong, J. Morgan, and N. M. Bleehen Diminished Expression of Insulin-like Growth Factor (IGF) Binding Protein-5 and Activation of IGF-I-mediated Autocrine Growth in Simian Virus 40-transformed Human Fibroblasts J. Biol. Chem., January 6, 1995; 270(1): 135 - 142. [Abstract] [Full Text] [PDF]

				J. P. Holden, T. L. Butzow, G. A. Laughlin, M. Ho, A. J. Morales, and S. C. Yen Regulation of Insulin-Like Growth Factor Binding Protein-I During the 24-Hour Metabolic Clock and in Response to Hypoinsulinemia Induced by Fasting and Sandostatin in Normal Women Reproductive Sciences, January 1, 1995; 2(1): 38 - 44. [Abstract] [PDF]

				K. Sakai, W. H. Busby Jr., J. B. Clarke, and D. R. Clemmons Tissue Transglutaminase Facilitates the Polymerization of Insulin-like Growth Factor-binding Protein-1 (IGFBP-1) and Leads to Loss of IGFBP-1's Ability to Inhibit Insulin-like Growth Factor-I-stimulated Protein Synthesis J. Biol. Chem., March 16, 2001; 276(12): 8740 - 8745. [Abstract] [Full Text] [PDF]