Skip to main content
Log in

Differential effect of fasting on IGF-BPs in serum of young and adult rats and its implication to impaired skin GAG content

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

During fasting or aging of animals there is a decreased content of skin glycosaminoglycans (GAGs). It has been found that the skin of adult rats contains about 60% of GAGs found in the skin of young animals. Fasting of both groups of animals (young and adult) resulted in decrease of GAG content. However, GAG content in the skin of fasted young rats decreased by 30% and in fasted adult rats by 15% only, compared to fed animals, respectively. The mechanism for the phenomena is not known. We considered insulin-like growth factor-I (IGF-I) as a potential candidate involved in regulation of GAG biosynthesis in both experimental models of animals. Adult rat sera were found to contain about 75% of IGF-I recovered from young rat sera. Fasting of both groups of animals resulted in dramatic decrease in serum IGF-I levels to about 50% of initial values. Since IGF-I activity and IGF-I serum half-life depends on the level of specific IGF-binding proteins (IGFBPs) we determined (i) relationship between main groups of IGFBPs, namely high molecular weight binding proteins (HMWBPs) and low molecular weight binding proteins (LMWBPs) and (ii) the amounts of IGF-I bound to respective proteins in the sera of all experimental animals. Control young rat serum was found to contain about 90% of HMWBPs and about 10% of LMWBPs as determined by ligand binding assay. In contrast, control adult rat serum contained about 60% of HMWBPs and about 40% of LMWBPs. Fasting of both groups of animals resulted in significant increase in serum levels of LMWBPs. Control young rat serum was found to contain about 8% IGF-I bound to LMWBPs while serum of control adult rats contained 18% IGF-I bound to these proteins. In sera of fasted young animals however, about 75% of the bound IGF-I was recovered from LMWBPs (about 60% of total serum IGF-I) while in sera of fasted adult animals only about 56% of the bound IGF-I was recovered from LMWBPs (about 50% of total serum IGF-I). Evidence was provided that during fasting of both groups of animals there is a significant decrease in serum BP-3 and dramatic increase in serum BP-1 concentrations, compared to respective controls. However, the concentration of BP-1 in serum of fasted young rats was increased by about 60 fold while in serum of fasted adult rats only by about 10 fold, compared to respective control animals. Negative correlation between skin GAG content and LMWBPs derived IGF-I during fasting of young (r = - 0.943, p < 0.001) and adult ( r = - 0.571, p < 0.01) rats was found.

The data presented suggest that the effects of aging and fasting on decreased skin GAG content may be due to induction of LMWBPs that are known to (i) inhibit IGF-I dependent function and (ii) increase clearance of IGF-I from circulation. However, the effects of fasting are distinct in respect to young and adult rats suggesting that mechanisms involved in regulation of IGF-I bioactivity during aging are more complex that during fasting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Wolańska M, Sobolewski K, Bańkowski E, Chyczewski L: Alterations in glycosaminoglycan composition of methylcholanthrene-induced sarcoma at various stages of the tumor growth. Folia Histochem Cytobiol 34: 21–26, 1996

    Google Scholar 

  2. Bańkowski E, Sobolewski K, Romanowicz L, Chyczewski L, Jaworski S: Collagen and glycosaminoglycans of Wharton's jelly and their alterations in EPH-gestosis. Eur J Obstet Gynecol Reprod Biol 66: 109–117, 1996

    Article  PubMed  Google Scholar 

  3. Romanowicz L, Bańkowski E, Galewska Z, Jaworski S: Glycosaminoglycan-biosynthesis in the wall of the umbilical cord artery and its alteration in EPH-gestosis. Eur J Obstet Gynecol Reprod Biol 72: 19–25, 1997

    Article  PubMed  Google Scholar 

  4. Cechowska-Pasko M, Pałka J, Bańkowski E: Decrease in the glycosaminoglycan content in the skin of diabetic rats. The role of IGF-I, IGF-binding proteins and proteolytic activity. Mol Cell Biochem 154: 1–8, 1996

    Article  PubMed  Google Scholar 

  5. Oyamada I, Pałka J, Schalk EM, Takeda K, Peterkofsky B: Scorbutic and fasted guinea pig sera contain an insulin-like growth factor I-reversible inhibitor of proteoglycan and collagen synthesis in chick embryo chondrocytes and adult human skin fibroblasts. Arch Biochem Biophys 276: 86–93, 1990

    Article  Google Scholar 

  6. Takeda K, Gosiewska A, Peterkofsky B: Similar but not identical, modulation of expression of extracellular matrix components during in vitro and in vivo aging of human skin fibroblasts. J Cell Physiol 153: 450–459, 1992

    Article  PubMed  Google Scholar 

  7. Van Wyk JJ: The somatomedins: Biological action and physiological control mechanisms. In: C.H. Li (ed). Hormonal Proteins and Peptides. Academic Press, New York, 1984, pp 81–125

    Google Scholar 

  8. Froesch ER, Zapf J: Insulin-like growth factors and insulin: Comparative aspects. Diabetologia 28: 485–493, 1985

    Article  PubMed  Google Scholar 

  9. Baxter RC, Martin JL: Binding proteins for insulin-like growth factors in adult rat serum. Comparison with other human and rat binding proteins. Biochem Biophys Res Commun 147: 408–415, 1987

    Article  PubMed  Google Scholar 

  10. Martin JL, Baxter RC: Insulin-like growth factor binding protein from human plasma. J Biol Chem 261: 8754–8760, 1986

    PubMed  Google Scholar 

  11. Baxter RC, Martin JL: Binding proteins for the insulin-like growth factors: Structure, regulation and function. Prog Growth Factor Res 1: 49–68, 1989

    Article  PubMed  Google Scholar 

  12. Lamson G, Giudice LC, Rosenfeld RG: Insulin-like growth factor binding protein: Structural and molecular relationships. Growth Factors 5: 19–28, 1991

    PubMed  Google Scholar 

  13. Blum WF, Jenne EW, Reppin JF, Kietzmann IT, Ranke MB, Bierich JR: Insulin-like growth factor-I (IGF-I)-binding protein complex is a better mitogen than free IGF-I. Endocrinology 125: 766–772, 1989

    PubMed  Google Scholar 

  14. Pałka J, Bird TA, Oyamada I, Peterkowsky B: Similar hormonal changes in sera from scorbutic and fasted (Vitamin C-supplemented) guinea pig, including decreased IGF-I and appearance of an IGF-I reversible mitogenic inhibitor. Growth Factors 1: 147–156, 1989

    PubMed  Google Scholar 

  15. Peterkofsky B, Pałka J, Wilson S, Takeda K, Shah V: Elevated activity of molecular weight insulin-like growth factor-binding proteins in sera of vitamin C-deficient and fasted guinea pigs. Endocrinology 128: 1769–1779, 1991

    PubMed  Google Scholar 

  16. Elgin RG, Busby WH, Clemmons DR: An insulin-like growth factor (IGF) binding protein enhances the biological response to IGF-I. Proc Natl Acad Sci USA 84: 3254–3258, 1987

    PubMed  Google Scholar 

  17. Rechler MM, Nissley SP: Peptide growth factors and their receptors. I Insulin-like growth factors. In: M.B. Sporn, A.B. Roberts (eds). Handbook of Experimental Pharmacology. Springer-Verlag, Berlin, 1990, pp 263–367

    Google Scholar 

  18. McCusker RH, Busby WH, Dehoff MH, Camacho-Hubner C, Clemmons DR: Insulin-like growth factor binding to cell monolayers is directly modulated by the addition of IGF-binding proteins. Endocrinology 129: 939–949, 1991

    PubMed  Google Scholar 

  19. Jones JI, Clemmons DR: Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16: 3–34, 1995

    Article  PubMed  Google Scholar 

  20. Rechler MM: Non-receptor binding proteins for insulin growth factors and other cytokines: Modulators of peptide action. In: B.D. Weintraub (ed). Molecular Endocrinology: Basic Concepts and Clinical Correlations. Raven Press, New York, 1994, pp 155–180

    Google Scholar 

  21. Arai T, Clarke J, Parker A, Busby W Jr, Nam T, Clemmons DR: Substitution of specific amino acids in insulin-like growth factor (IGF) binding protein 5 alters heparin binding and its change in affinity for IGF-I in response to heparin. J Biol Chem 271: 6099–6106, 1996

    Article  PubMed  Google Scholar 

  22. Wosicki A: Glycosaminoglycans of human chorion in the first trimester of embryonal development. Gin Pol 45: 1055–1060, 1974

    Google Scholar 

  23. Bitter T, Muir HM: A modified uronic acid carbazole reaction. Anal Biochem 4: 330–334, 1962

    Article  PubMed  Google Scholar 

  24. Pałka J, Peterkofsky B: Salt stimulation of serum insulin-like growth factor binding protein activity. Anal Biochem 175: 442–449, 1988

    Article  PubMed  Google Scholar 

  25. Mosses AC, Nissley SP, Short PA, Rechler MM, White RM, Knight AB, Higa OZ: Increased levels of multiplication-stimulating activity, an insulin-like growth factor in fetal rat serum. Proc Natl Acad Sci USA 77: 3649–3656, 1980

    PubMed  Google Scholar 

  26. Miles LEM, Lipschitz DA, Bieber CP, Cook JD: Measurement of serum ferritin by a 2-site immunoradiometric assay. Anal Biochem 61: 209–224, 1974

    Article  PubMed  Google Scholar 

  27. Gosiewska A, Wilson S, Kwon D, Peterkofsky B: Evidence for in vivo role of insulin-like growth factor-binding protein-1 and-2 as inhibitors of collagene gene expression in vitamin C-deficient and fasted guinea pigs. Endocrinology 134: 1329–1339, 1994

    Article  PubMed  Google Scholar 

  28. Daughaday WH, Hall K, Salmon WD, van den Brand JL, van Wyk JJ: On the nomenclature of the somatomedins and insulin-like growth factors. J Clin Endocrinol Metab 65: 1075–1076, 1987

    PubMed  Google Scholar 

  29. Clemons DR: Insulin-like growth factor binding proteins and their role in controlling IGF actions. Cytokine Growth Factor Rev 8: 45–62, 1997

    Article  PubMed  Google Scholar 

  30. Lewitt MS, Denyer GS, Cooney GJ, Baxter RC: Insulin-like growth factor-binding protein-1 modulates blood glucose levels. Endocrinology 129: 2254–2256, 1991

    PubMed  Google Scholar 

  31. Guler HP, Zapf J, Froesch ER: Short-term metabolic effects of recombinant human insulin-like growth factor-I in healthy adults. N Engl J Med 317: 137–140, 1987

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cechowska-Pasko, M., Pałka, J. Differential effect of fasting on IGF-BPs in serum of young and adult rats and its implication to impaired skin GAG content. Mol Cell Biochem 205, 45–52 (2000). https://doi.org/10.1023/A:1007076809488

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007076809488

Navigation