Skip to main content

Advertisement

Log in

Differential effects of insulin and insulin-like growth factor-I in the femoral tissues of rats with skeletal unloading

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

The alteration of bone metabolism in the femur of rats with skeletal unloading for 4 days was investigated. Skeletal unloading was designed using the model of hindlimb hang in rats. Skeletal unloading caused a significant decrease in femoral weight, calcium, and phosphorus contents in the metaphysis but not diaphysis. Also, the unloading induced a significant decrease of zinc content, alkaline phosphatase activity, and deoxyribonucleic acid (DNA) content in the femoral diaphysis and metaphysis. When the femoraldiaphyseal and metaphyseal tissues from normal and skeletal-unloading rats were cultured in the presence of insulin (10-9 and 10-8 M) for 24 hours in vitro, the hormonal effect to increase alkaline phosphatase activity and DNA content in the diaphysis, but not metaphysis, was lost in the bone tissues from unloading rats. However, the culture with insulin-like growth factor-I (IGF-I; 10-8 and 10-7 M) produced a significant increase of alkaline phosphatase activity and DNA content in both the diaphyseal and metaphyseal tissues from normal and unloading rats. These results demonstrate that skeletal unloading causes an impairment of insulin effect, but not IGF-I effect, on bone metabolism in femoral tissues.

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. Heaney RP (1962) Radiocalcium metabolism in tissue osteoporosis in man. Am J Med 33:188–194

    Google Scholar 

  2. Morey ER, Baylink DJ (1978) Inhibition of bone formation during spaceflight. Science 202:1138–1141

    Google Scholar 

  3. Donaldson CL, Hulley SB, Vogel JM, Hattner RS, Bayers JH, McMillan DE (1970) Effect of prolonged bed rest on bone mineral. Metabolism 19:1071–1077

    Google Scholar 

  4. Globus RK, Bikle DD, Morey-Holton ER (1984) Effects of simulated weightlessness on bone mineral metabolism. Endocrinology 114:2264–2270

    Google Scholar 

  5. Globus RK, Bikle DD, Morey-Holton ER (1986) The temporal response of bone to unloading. Endocrinology 118:733–742

    Google Scholar 

  6. Jaworsky ZFG, Uhthoff HK (1986) Reversibility of nontraumatic disease osteoporosis during its active phase. Bone 7:431–439

    Google Scholar 

  7. Yamaguchi M, Ozaki K, Hoshi T (1989) Simulated weightlessness and bone metabolism: decrease of alkaline phosphatase activity in the femoral diaphysis of rats. Res Exp Med 189:9–14

    Google Scholar 

  8. Yamaguchi M, Ozaki K, Hoshi T (1989) Simulated weightlessness and bone metabolism: decreases of protein and DNA syntheses in the femoral diaphysis of rats. Res Exp Med 189:331–337

    Google Scholar 

  9. Yamaguchi M, Ozaki K, Hoshi T (1991) Simulated weightlessness and bone metabolism: impairment of glucose consumption in bone tissue. Res Exp Med 191:105–111

    Google Scholar 

  10. Yamaguchi M, Sakurai T, Ohtaki J, Hoshi T (1991) Simulated weightlessness and bone metabolism: evidence for direct gravitational effect and its related insulin action. Res Exp Med 191: 273–280

    Google Scholar 

  11. Levy JR, Murray E, Manolagas S, Olefsky JM (1986) Demonstration of insulin receptors and modulation of alkaline phosphatase activity by insulin in rat osteoblastic cells. Endocrinology 119:1786–1792

    Google Scholar 

  12. Kream BE, Swith MD, Canalis E, Raisz LG (1985) Characterization of the effect of insulin on collagen synthesis in fetal rat bone. Endocrinology 116:296–302

    Google Scholar 

  13. Hock JM, Centrella M, Canalis E (1988) Insulin-like growth factor has independent effects on bone matrix formation and cell replication. Endocrinology 122:254–260

    Google Scholar 

  14. Schmid C, Guler HP, Rowe D, Froesch ER (1989) Insulin-like growth factor I regulates type I procollagen mRNA steady state levels in bone of rats. Endocrinology 125:1575–1580

    Google Scholar 

  15. Canalis E, Pash J, Gabbitas B, Rydziel S, Varghese S (1993) Growth factors regulate the synthesis of insulin-like growth factor-I in bone cell cultures. Endocrinology 133:33–38

    Google Scholar 

  16. Taussky HH, Shon E (1953) A microcolorimetoric method for the determination of inorganic phosphorus. J Biol Chem 202: 675–685

    Google Scholar 

  17. Walter K, Schutt C (1965) Acid and alkaline phosphatase in serum. In: Bergmeyer HU (ed) Methods of enzymatic analysis, vols 1 and 2. Academic Press, New York, pp 856–860

    Google Scholar 

  18. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–273

    Google Scholar 

  19. Flanagan B, Nichols G Jr (1962) Metabolic studies of bone in vitro. IV. Collagen biosynthesis by surviving bone fragments in vitro. J Biol Chem 237:3786–3792

    Google Scholar 

  20. Ceriotti G (1955) Determination of nucleic acids in animal tissues. J Biol Chem 214:39–77

    Google Scholar 

  21. Bikle DD, Halloran BP, Cone CM, Globus RK, Morey-Holton E (1987) The effects of simulated weightlessness on bone maturation. Endocrinology 120:678–684

    Google Scholar 

  22. Sessions NV, Halloran BP, Bikle DD, Wronski TJ, Cone C, Morey-Holton E (1989) Bone response to normal weight bearing after a period of skeletal unloading. Am J Physiol 257:E606-E610

    Google Scholar 

  23. Machwate M, Zerath E, Holy X, Pastoureau P, Marie PJ (1994) Insulin-like growth factor-I increases trabecular bone formation and osteoblastic cell proliferation in unloaded rats. Endocrinology 134:1031–1038

    Google Scholar 

  24. Halloran BP, Bikle DD, Wronski TJ, Globus RK, Levans MJ, Morey-Holton ER (1986) The role of 1,25-dihydroxy vitamin D in the inhibition of bone formation induced by skeletal unloading. Endocrinology 118:948–954

    Google Scholar 

  25. Yamaguchi M, Oishi H, Suketa Y (1987) Stimulatory effect of zinc on bone formation in tissue culture. Biochem Pharmacol 36:4007–4012

    Google Scholar 

  26. Yamaguchi M, Ozaki K, Hoshi T (1991) Simulated weightlessness and bone metabolism: impairment of insulin effect on alkaline phosphatase activity in bone tissue. Res Exp Med 191: 113–119

    Google Scholar 

  27. Yamaguchi M, Hoshi T (1992) Simulated weightlessness and bone metabolism: gravitational stimulation enhances insulin sensitivity. Res Exp Med 192:345–353

    Google Scholar 

  28. Shinar DM, Endo N, Halperin D, Rodan GA, Weinreb M (1993) Differential expression of insulin-like growth factor-I (IGF-I) and IGF-II messenger ribonucleic acid in growing rat bone. Endocrinology 132:1158–1167

    Google Scholar 

  29. Pfeilschifter J, Oechsner M, Naumann A, Gronwald RGK, Minne HW, Ziegler R (1990) Stimulation of bone matrix apposition in vitro by local growth factors: a comparison between insulin-like growth factor I, platelet-derived growth factor, and transforming growth factor β. Endocrinology 127:69–75

    Google Scholar 

  30. Burch RE, Hahn HK, Sullivan JF (1975) Newer aspects of the roles of the zinc, manganese, and copper in human nutrition. Clin Chem 21:501–520

    Google Scholar 

  31. Yamaguchi M, Yamaguchi R (1986) Action of zinc on bone metabolism in rats. Increases in alkaline phosphatase activity and DNA content. Biochem Pharmacol 35:773–777

    Google Scholar 

  32. Yamaguchi M, Oishi H, Suketa Y (1988) Zinc stimulation of bone protein synthesis in tissue culture. Activation of aminoacyl-tRNA synthetase. Biochem Pharmacol 37:4075–4080

    Google Scholar 

  33. Hurley LS, Gowan J, Milhaud G (1969) Calcium metabolism in manganese-deficient and zinc-deficient rats. Proc Soc Exp Biol Med 130:856–860

    Google Scholar 

  34. Oner G, Bhaumick B, Bala RM (1984) Effect of zinc deficiency on serum somatomedin levels and skeletal growth in young rats. Endocrinology 114:1860–1863

    Google Scholar 

  35. Hashizume M, Yamaguchi M (1993) Stimulatory effect of β-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells. Mell Cell Biochem 122:59–64

    Google Scholar 

  36. Yamaguchi M, Hashizume M (1994) Effect of β-alanyl-L-histidinato zinc on protein components in osteoblastic MC3T3-E1 cells: increases in osteocalcin insulin-like growth factor-I and transforming growth factor-β. Mol Cell Biochem (in press).

  37. Higashi A, Nakamura T, Nishigawa S, Matsukura M, Tomoeda S, Futagoishi Y, Shinohara M, Matsuda I (1993) J Am Coll Nutr 12:61–65

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamaguchi, M., Kishi, S. Differential effects of insulin and insulin-like growth factor-I in the femoral tissues of rats with skeletal unloading. Calcif Tissue Int 55, 363–367 (1994). https://doi.org/10.1007/BF00299316

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00299316

Key words

Navigation