Pharmaceutical Research

, Volume 11, Issue 2, pp 226–230 | Cite as

Colonic Absorption of Insulin-like Growth Factor I in Vitro

  • Elizabeth Quadros
  • Nancy M. Landzert
  • Sheryl LeRoy
  • Francis Gasparini
  • Gregory Worosila


Colonic absorption of recombinant human insulin-like growth factor I (rhIGF-I) was measured in vitro using both rat and minipig colon. The permeability coefficients were 8.03 ± 1.03 and 4.75 ± 0.43 × 10−8 cm sec−1 in the rat and minipig, respectively. The steady-state flux in rat colon was linearly related to the donor concentration over the range 1 to 10 mg/mL. rhIGF-I was metabolically stable in contact with both mucosal and serosal surfaces of washed colon for 5 hr. The amount of IGF-I permeating through the tissue was quantitated by radioimmunoassay and the identity and integrity of the permeating species were confirmed by reverse-phase HPLC, sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and Western blotting. In all cases the permeant was identical to authentic rhIGF-I. The integrity of the colonic tissue in vitro was demonstrated by the maintenance of electrophysiological parameters, a secretory response to serosal theophylline, and the ability of sodium azide, a metabolic inhibitor, to abolish the barrier properties and cause a large increase in flux.

insulin-like growth factor I colon drug delivery protein absorption 


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  1. 1.
    E. Rinderknecht and R. E. Humbel. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J. Biol. Chem. 253:2769–2776 (1978).Google Scholar
  2. 2.
    S. Gammeltoft. Insulin-like growth factors and insulin: Gene expression, receptors, and biological actions. In J. Martinez (ed.), Peptide Hormones as Prohormones: Processing, Biological Activity, Pharmacology, Halsted Press, New York, 1989.Google Scholar
  3. 3.
    V. R. Sara and K. Hall. Insulin-like growth factors and their binding proteins. Physiol. Rev. 70:591–614 (1990).Google Scholar
  4. 4.
    S. Hardouin, P. Hossenlopp, B. Segouia, D. Seurin, G. Portolan, C. Lassame, and M. Binoux. Heterogeneity of insulin-like growth factor binding proteins and relationships between structure and affinity. I. Circulating forms in man. Eur. J. Biochem. 170:121–132 (1987).Google Scholar
  5. 5.
    P. E. Walton, R. Gopinath, B. D. Burleigh, and T. D. Etherton. Administration of recombinant human insulin-like growth factor I to pigs: Determination of circulating half-lives and chromatographic profiles. Horm. Res. 31:138–142 (1989).Google Scholar
  6. 6.
    S. C. Hodgkinson, S. R. Davis, B. D. Burleigh, H. V. Henderson, and P. D. Gluckman. Metabolic clearance rate of insulin-like growth factor-I in fed and starved sheep. J. Endocr. 115:233–240 (1987).Google Scholar
  7. 7.
    D. S. Schalch, N. J. Turman, V. Marcsisin, and H. P. Guler. Short-term metabolic effects of recombinant human insulin-like growth factor I (rhIGF-I) in type II diabetes mellitus. 2nd International IGF Symposium on Insulin-Like Growth Factors/Somatomedins, 1991.Google Scholar
  8. 8.
    A. Giacca, R. Gupta, S. Efendic, K. Hall, A. Skottner, L. Lickley, and M. Vranic. Differential effects of IGF-I and insulin on glucoregulation and fat metabolism in depancreatized dogs. Diabetes 39:340–347 (1990).Google Scholar
  9. 9.
    F. M. Tomas, S. E. Knowles, P. C. Owens, L. C. Read, C. S. Chandler, S. E. Gargosky, and F. J. Ballard. Increased weight gain, nitrogen retention and muscle protein synthesis following treatment of diabetic rats with insulin-like growth factor (IGF-I) and des(1–3)IGF-I. Biochem. J. 276:547–554 (1992).Google Scholar
  10. 10.
    E. M. Spencer, C. C. Liu, E. C. C. Si, and G. A. Howard, In vivo actions of insulin-like growth factor-I (IGF-I) on bone formation and resorption in rats. Bone 12:21–26 (1991).Google Scholar
  11. 11.
    S. A. W. Gibson, C. McFarlan, S. Hay, and G. T. MacFarlane. Significance of microflora in proteolysis in the colon. Appl. Env. Microbiol. 55:679–683 (1989).Google Scholar
  12. 12.
    M. Proano, M. Camilleri, S. F. Phillips, M. L. Brown, and G. M. Thomforde. Transit of solids through the human colon: Regional quantification in the unprepared bowel. Am. J. Physiol. 258:G856–G862 (1990).Google Scholar
  13. 13.
    B. Krevsky, L. S. Malmud, F. D'Ercole, A. H. Maurer, and R. S. Fisher. Colonic transit scintigraphy. A physiological approach to the quantitative measurement of colonic transit in humans. Gastroenterology 91:1102–1112 (1986).Google Scholar
  14. 14.
    V. S. Chadwick, S. F. Phillips, and A. F. Hofmann. Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). II. Application to normal and abnormal permeability states in man and animals. Gastroenterology 73:247–251 (1977).Google Scholar
  15. 15.
    M. L. G. Gardner. Gastrointestinal absorption of intact proteins. Annu. Rev. Nutr. 8:329–350 (1988).Google Scholar
  16. 16.
    A. L. Warshaw, C. A. Bellini, and W. A. Walker. The intestinal mucosal barrier to intact antigenic protein. Difference between colon and small intestine. Am. J. Surg. 133:55–58 (1977).Google Scholar
  17. 17.
    J. Hastewell, S. Lynch, I. Williamson, R. Fox, and M. Mackay. Absorption of human calcitonin across the rat colon in vivo. Clin. Sci. 82:589–594 (1992).Google Scholar
  18. 18.
    A. N. Elias, I. Gordon, N. D. Vaziri, G. Chune, M. R. Pandian, G. Gwinup, and R. Wesley. Effective portal insulin delivery with enzyme-protected capsules in pancreatectomized pigs. Gen. Pharmac. 23:55–59 (1992).Google Scholar
  19. 19.
    E. Quadros, J. Cassidy, K. Gniecko, and S. LeRoy. Buccal and colonic absorption of CGS 16617, a novel ACE inhibitor. J. Control. Release 19:77–86 (1991).Google Scholar
  20. 20.
    G. Parsons and C. R. Paterson. Fluid and solute transport across rat colonic mucosa. Q. J. Exp. Physiol. 50:220–231 (1965).Google Scholar
  21. 21.
    R. J. Schilling and A. K. Mitra. Intestinal transports of insulin. Int. J. Pharm. 62:53–64 (1990).Google Scholar
  22. 22.
    B. Matuszewska, G. G. Liversidge, F. Ryan, J. Dent, and P. L. Smith. In vitro study of intestinal absorption and metabolism of 8-L-arginine vasopressin and its analogues. Int. J. Pharm. 46:111–120 (1988).Google Scholar
  23. 23.
    N. M. Landzert, K. Gniecko, and E. Quadros. Protein digestion in the gastrointestinal tract. Pharm. Res. 9:S179 (1992).Google Scholar
  24. 24.
    M. Laburthe, C. Rouyer-Fessard, and S. Gammeltoft. Receptors for insulin-like growth factors I and II in rat gastrointestinal epithelium. Am. J. Physiol. 254:G457–G462 (1988).Google Scholar
  25. 25.
    B. Termanini, R. V. Nardi, T. M. Finan, I. Parikh, and L. Y. Korman. Insulin-like growth factor I receptors in rabbit gastrointestinal tract. Gastroenterology 99:51–60 (1990).Google Scholar
  26. 26.
    J. A. McRoberts, R. Aranda, N. Riley, and H. Kang. Insulin regulates the paracellular permeability of cultured intestinal epithelial cell monolayers. J. Clin. Invest. 85:1127–1134 (1990).Google Scholar
  27. 27.
    J. A. McRoberts, N. Riley, R. Aranda, and H. Kang. Regulation of colonic epithelial cell tight junction permeability by insulin-like growth factors. 2nd International Symposium on Insulin-like Growth Factors/Somatomedins, 1991.Google Scholar
  28. 28.
    M. Narawane and V. H. L. Lee. Growth factors as penetration enhancers for transepithelial protein transport. Pharm. Res. 9:S-242 (1992).Google Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Elizabeth Quadros
    • 1
  • Nancy M. Landzert
    • 1
  • Sheryl LeRoy
    • 2
  • Francis Gasparini
    • 2
  • Gregory Worosila
    • 2
  1. 1.Pharmaceutical DivisionCiba-Geigy CorporationArdsley
  2. 2.Pharmaceutical DivisionCiba-Geigy CorporationSuffern

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