Journal of Bone and Mineral Metabolism

, Volume 11, Supplement 1, pp S30–S37 | Cite as

Effects of 7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one (ipriflavone) on serum levels of calcitonin and parathyroid hormone in patients with adult-onset diabetes

  • Kiyoshi Hashizume
  • Kazuo Ichikawa
  • Satoru Suzuki
  • Teiji Takeda
  • Mutsuhiro Kobayashi
  • Yutaka Nishii
  • Xiao-Yun Ma
Section II: Internal Medicine


The effects of 1α-hydroxycholecalciferol [1α(OH)D3] and 7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one [ipriflavone (IP)] on the serum concentrations of parathyroid hormone (PTH) and calcitonin (CTN) were studied in patients with adult-onset diabetes (NIDDM). A group of 122 NIDDM patients with unrestricted caloric intake were divided by random sampling into dietary (D) and non-dietary (ND) groups. Group D was placed on a calorie-restricted diet while group ND remained free of dietary restrictions. Two years after the groups were so divided, the groups were further divided by random sampling into 2 sub-groups (D1 and D2; ND1 and ND2). Groups D1 and ND1 received 1α(OH)D3 for 2 months, followed by combined IP/1α(OH)D3 administration for 6 months, and groups D2 and ND2 received a placebo in place of 1α(OH)D3. Serum PTH levels were higher and serum CTN levels were lower in group D than in group ND. Administration of 1α(OH)D3 to group D1 patients decreased serum PTH levels and increased serum calcium concentration, although serum CTN levels were not affected. Serum CTN levels were found to increase significantly (p<0.01), without changes in serum PTH concentrations, during the 6 months, combination treatment of 1α(OH)D3 and IP. IP also increased CTN levels in group ND2 and in patients in group D2 who had no prior 1α(OH)D3 treatment. IP did not, however, increase serum CTN levels significantly in patients whose serum PTH concentration was relatively high (500 pg/ml or more). These results suggest that IP is suitable for increasing serum CTN levels in NIDDM patients, and that its action is dependent on serum PTH levels.

Key words

Parathyroid hormone Calcitonin Ipriflavone Vitamin D3 Adult-onset diabetes mellitus 


  1. 1.
    Flood TM, Halford BN, Cooppan R, et al. Dietary management of diabetes. In: Marble A, Krall LP, Bradley RE, et al. eds. Joslin’s Diabetes Mellitus. 12th Edition, Lea & Febiger, Philadelphia, 1985:357–372Google Scholar
  2. 2.
    Hough S, Russell JF, Teitelbaum SL, et al. Calcium homeostasis in chronic streptozotocin-induced diabetes mellitus in the rat. Am J Physiol 1982;242:E451-E456PubMedGoogle Scholar
  3. 3.
    Hashizume K, Ichikawa K, Suzuki S, Takeda T, Yamauchi K, Kobayashi M. Calorie restriction increases serum parathyroid hormone and decreases serum calcitonin levels in patients with maturity onset diabetes mellitus. J Bone Miner Metab 1992 (in press)Google Scholar
  4. 4.
    Yamazaki I, Shino A, Shimizu Y, et al. Effect of Ipriflavone on glucocorticoid-induced osteoporosis in rats. Life Sci 1986;38:951–958PubMedGoogle Scholar
  5. 5.
    Yamazaki I, Shino A, Tsukada R. Effect of ipriflavone on osteoporosis induced by ovariectomy in rats. J Bone Miner Metab 1986;3:205–210Google Scholar
  6. 6.
    Shino A, Matsuo T, Tsuda M, Yamazaki I, Tsukada R, Kitazaki T, Shiota K, Odaka H, Yoshida K. Effects of ipriflavone on bone and mineral metabolism in the streptozotocin rats. J Bone Miner Metab 1986;3:177–187Google Scholar
  7. 7.
    Hruska KA, Kopelman R, Rutherford WE, et al. Metabolism of immunoreactive parathyroid hormone in dogs: The role of the kidney and the effects of chronic renal failure. J Clin Invest 1975;56:39–48PubMedGoogle Scholar
  8. 8.
    Eisman JA, Hamstra AJ, Kream BE, et al. 1,25-dihydroxyvitamin D in biological fluids: A simplified and sensitive assay. Science 1976;193:1021–1023PubMedGoogle Scholar
  9. 9.
    Menard L, Dempsey ME, Blankstein LA, et al. Quantitative determination of glycosylated hemoglobin A1 by agar gel electrophoresis. Clin Chem 1980;26:1598–1602PubMedGoogle Scholar
  10. 10.
    Mayer GP, Hurst JG. Sigmoidal relationship between parathyroid hormone secretion rate and plasma calcium concentration in calves. Endocrinology 1978;102:1036–1042PubMedGoogle Scholar
  11. 11.
    Mayer GP, Keaton JA, Hurst JG, Habener JE. Effects of plasma calcium concentration on the relative proportion of hormone and carboxy fragments in parathyroid venous blood. Endocrinology 1979;104:1778–1784PubMedGoogle Scholar
  12. 12.
    Tucker G III, Gagnon RE, Haussler MR. Vitamin D3-25-hydroxylase: Tissue occurrence and apparent lack of regulation. Arch Biochem Biophys 1973;155:47–57PubMedGoogle Scholar
  13. 13.
    Gallagher JC, Jerpbak CM, Jee WSS, Johnson KA, DeLuca HF, Riggs BL. 1,25-dihydroxy-vitamin D3: Short- and long-term effects on bone and calcium metabolism in patients with post-menopausal osteoporosis. Proc Natl Acad Sci USA 1982;79:3325–3329PubMedGoogle Scholar
  14. 14.
    Nordin BEC, Horsman A, Crily RG, Marshall DH, Simpson M. Treatment of spinal osteoporosis in postmenopausal women. Br Med J 1980;280:451–453PubMedGoogle Scholar
  15. 15.
    Bouillon R, Van Assche FA, Van Baelen H, Heyns W, De Moor P. Influence of the vitamin-D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3: Significance of the free 1,25-dihydroxyvitamin D3 concentration. J Clin Invest 1981;67:589–596PubMedGoogle Scholar
  16. 16.
    Bikkle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 1986;63:954–959Google Scholar
  17. 17.
    Vanham G, Van Baelen H, Tan BK, et al. The effect of vitamin D analogs and of vitamin-D-binding protein on lymphocyte proliferation. J Steroid Biochem 1988;29:381–386CrossRefPubMedGoogle Scholar
  18. 18.
    Dietel M, Dorn G, Montz R, Altenahr E. Influence of vitamin D3, 1,25-dihydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 on para-thyroid hormone secretion, adenosine 3′,5′-mono-phosphate release, and ultrastructure of para-thyroid glands in organ culture. Endocrinology 1979;105:237–245PubMedGoogle Scholar
  19. 19.
    Chertow BS, Baker GR, Henry HL, Norman AW. Effects of vitamin D metabolites on bovine parathyroid hormone secretion from bovine parathyroid cells in tissue culture. Endocrinology 1985;117:2114–2119Google Scholar
  20. 20.
    Cantley LK, Russell J, Lettieri D, Sherwood LM. 1,25-dihydroxyvitamin D3 suppresses parathyroid hormone secretion from bovine parathyroid cells in tissue culture. Endocrinology 1985;117:2114–2119PubMedGoogle Scholar
  21. 21.
    Delmez JA, Tindira C, Grooms P, et al. Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D: A role for increased sensitivity to calcium. J Clin Invest 1989;83:1349–1355PubMedGoogle Scholar
  22. 22.
    Freake HC, MacIntyre I. Specific binding of 1,25-dihydroxycholecalciferol in human medullary thyroid carcinoma. Biochem J 1982;206:181–184PubMedGoogle Scholar
  23. 23.
    Copp DH, Cameron EC, Cheney BA, Davidson AGF, Henze KG. Evidence for calcitonin—a new hormone from the parathyroid that lowers blood calcium. 1962;70:638–649Google Scholar
  24. 24.
    Kumar MA, Foster GV, MacIntyre I. Further evidence for calcitonin, a rapid-acting hormone which lowers plasma calcium. Lancet 1963;2:480–482Google Scholar
  25. 25.
    Yamazaki I. Effect of ipriflavone on accessory sexual orgams and bone metabolism in male rats. Bone and Mineral 1987;2:271–280PubMedGoogle Scholar
  26. 26.
    Yamazaki I, Kinoshita M. Calcitonin secreting property of ipriflavone in the presence of estrogen. Life Sci 1986;38:1535–1541PubMedGoogle Scholar
  27. 27.
    Bradbury RB, White DE. Estrogen and related substances in plants. Vitam Horm (NY) 1954;23:207–233Google Scholar
  28. 28.
    Atkins D, Peacock M. A comparison of the response of bone to parathyroid hormone in tissue culture. J Endocrinol 1975;64:573–583PubMedGoogle Scholar
  29. 29.
    First BP, Miller M, Deftos LJ. Effects of oophorectomy (OOPHX) and estrogen replacement on calcitonin levels in sexually mature female rats. Calcif Tissue Int 1981;33:304Google Scholar
  30. 30.
    Stevenson JC, Abeyasekara GA, Hillyard CJ, et al. Hormones in postmenopausal women: Effects of estrogens. Lancet 1981;1:693–695PubMedGoogle Scholar

Copyright information

© Japanese Society of Bone Metabolism Research 1993

Authors and Affiliations

  • Kiyoshi Hashizume
    • 1
  • Kazuo Ichikawa
    • 1
  • Satoru Suzuki
    • 1
  • Teiji Takeda
    • 1
  • Mutsuhiro Kobayashi
    • 1
  • Yutaka Nishii
    • 1
  • Xiao-Yun Ma
    • 1
  1. 1.Department of Geriatrics, Endocrinology and MetabolismShinshu University School of MedicineMatsumotoJapan

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