Advertisement

The Journal of Physiological Sciences

, Volume 67, Issue 1, pp 71–81 | Cite as

Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption

  • Kannikar Wongdee
  • Nateetip Krishnamra
  • Narattaphol CharoenphandhuEmail author
Review

Abstract

Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D3, and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring.

Keywords

Bone loss Calcium wasting Growth plate T1DM T2DM Osteoporosis 

Notes

Acknowledgments

Our research was supported by grants from the Cluster and Program Management Office (CPMO), National Science and Technology Development Agency (P-11-00639 to NK and P-13-00100 to NC), the Thailand Research Fund (TRF)–Mahidol University through the TRF Senior Research Scholar Grant (RTA5780001 to NC), the Faculty of Allied Health Sciences, Burapha University and TRF through TRF Research Scholar Award Grant (RSA5780041 to KW), the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission (6/2559 to KW).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. 1.
    American Diabetes Association (2014) Diagnosis and classification of diabetes mellitus. Diabetes Care 37(Suppl 1):S81–S90CrossRefGoogle Scholar
  2. 2.
    American Diabetes Association (2015) 2. Classification and diagnosis of diabetes. Diabetes Care 38(Suppl):S8–S16CrossRefGoogle Scholar
  3. 3.
    Isfort M, Stevens SC, Schaffer S, Jong CJ, Wold LE (2014) Metabolic dysfunction in diabetic cardiomyopathy. Heart Fail Rev 19:35–48PubMedCrossRefGoogle Scholar
  4. 4.
    Deli G, Bosnyak E, Pusch G, Komoly S, Feher G (2013) Diabetic neuropathies: diagnosis and management. Neuroendocrinology 98:267–280PubMedCrossRefGoogle Scholar
  5. 5.
    Reidy K, Kang HM, Hostetter T, Susztak K (2014) Molecular mechanisms of diabetic kidney disease. J Clin Invest 124:2333–2340PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Mlinar B, Marc J, Janez A, Pfeifer M (2007) Molecular mechanisms of insulin resistance and associated diseases. Clin Chim Acta 375:20–35PubMedCrossRefGoogle Scholar
  7. 7.
    Powers AC (2013) Diabetes mellitus. In: Jameson JL (ed) Harrison’s endocrinology, 3rd edn. McGraw-Hill, New York, pp 261–307Google Scholar
  8. 8.
    Samuel VT, Shulman GI (2012) Mechanisms for insulin resistance: common threads and missing links. Cell 148:852–871PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Hienz SA, Paliwal S, Ivanovski S (2015) Mechanisms of bone resorption in periodontitis. J Immunol Res 2015:615486PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Rayanagoudar G, Hashi AA, Zamora J, Khan KS, Hitman GA, Thangaratinam S (2016) Quantification of the type 2 diabetes risk in women with gestational diabetes: a systematic review and meta-analysis of 95,750 women. Diabetologia 59:1403–1411PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Committee on Practice Bulletins-Obstetrics (2013) Practice bulletin no. 137: gestational diabetes mellitus. Obstet Gynecol 122:406–416CrossRefGoogle Scholar
  12. 12.
    Kwak SH, Choi SH, Jung HS, Cho YM, Lim S, Cho NH, Kim SY, Park KS, Jang HC (2013) Clinical and genetic risk factors for type 2 diabetes at early or late post partum after gestational diabetes mellitus. J Clin Endocrinol Metab 98:E744–E752PubMedCrossRefGoogle Scholar
  13. 13.
    Kovacs CS (2016) Maternal mineral and bone metabolism during pregnancy, lactation, and post-weaning recovery. Physiol Rev 96:449–547PubMedCrossRefGoogle Scholar
  14. 14.
    Charoenphandhu N, Wongdee K, Krishnamra N (2010) Is prolactin the cardinal calciotropic maternal hormone? Trends Endocrinol Metab 21:395–401PubMedCrossRefGoogle Scholar
  15. 15.
    McDonald TJ, Ellard S (2013) Maturity onset diabetes of the young: identification and diagnosis. Ann Clin Biochem 50:403–415PubMedCrossRefGoogle Scholar
  16. 16.
    Anık A, Çatlı G, Abacı A, Böber E (2015) Maturity-onset diabetes of the young (MODY): an update. J Pediatr Endocrinol Metab 28:251–263PubMedGoogle Scholar
  17. 17.
    White BA (2010) Hormonal regulation of calcium and phosphate metabolism. In: Koeppen BM, Stanton BA (eds) Berne & Levy physiology, 6 (updated edition) edn. Mosby, St Louis, pp 696–705Google Scholar
  18. 18.
    Favus MJ, Goltzman D (2008) Regulation of cacium and magnesium. In: Rosen CJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 7th edn. American Society for Bone and Mineral Research, Washington, D.C., pp 104–108Google Scholar
  19. 19.
    Khuituan P, Teerapornpuntakit J, Wongdee K, Suntornsaratoon P, Konthapakdee N, Sangsaksri J, Sripong C, Krishnamra N, Charoenphandhu N (2012) Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D3-enhanced duodenal calcium transport in male mice. Am J Physiol Endocrinol Metab 302:E903–E913PubMedCrossRefGoogle Scholar
  20. 20.
    Khuituan P, Wongdee K, Jantarajit W, Suntornsaratoon P, Krishnamra N, Charoenphandhu N (2013) Fibroblast growth factor-23 negates 1,25(OH)2D3-induced intestinal calcium transport by reducing the transcellular and paracellular calcium fluxes. Arch Biochem Biophys 536:46–52PubMedCrossRefGoogle Scholar
  21. 21.
    Wongdee K, Teerapornpuntakit J, Sripong C, Longkunan A, Chankamngoen W, Keadsai C, Kraidith K, Krishnamra N, Charoenphandhu N (2016) Intestinal mucosal changes and upregulated calcium transporter and FGF-23 expression during lactation: contribution of lactogenic hormone prolactin. Arch Biochem Biophys 590:109–117PubMedCrossRefGoogle Scholar
  22. 22.
    Heath H 3rd, Lambert PW, Service FJ, Arnaud SB (1979) Calcium homeostasis in diabetes mellitus. J Clin Endocrinol Metab 49:462–466PubMedCrossRefGoogle Scholar
  23. 23.
    Yang Y, Zhang X, Bao M, Liu L, Xian Y, Wu J, Li P (2016) Effect of serum 25-hydroxyvitamin D3 on insulin resistance and β-cell function in newly diagnosed type 2 diabetes patients. J Diabetes Investig 7:226–232PubMedCrossRefGoogle Scholar
  24. 24.
    Chiu KC, Chu A, Go VL, Saad MF (2004) Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. Am J Clin Nutr 79:820–825PubMedCrossRefGoogle Scholar
  25. 25.
    Reis JP, Selvin E, Pankow JS, Michos ED, Rebholz CM, Lutsey PL (2016) Parathyroid hormone is associated with incident diabetes in white, but not black adults: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Metab 42:162–169PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Rivoira M, Rodríguez V, López MP, Tolosa de Talamoni N (2015) Time dependent changes in the intestinal Ca2+ absorption in rats with type I diabetes mellitus are associated with alterations in the intestinal redox state. Biochim Biophys Acta 1852:386–394PubMedCrossRefGoogle Scholar
  27. 27.
    Schneider LE, Schedl HP (1972) Diabetes and intestinal calcium absorption in the rat. Am J Physiol 223:1319–1323PubMedGoogle Scholar
  28. 28.
    Schneider LE, Nowosielski LM, Schedl HP (1977) Insulin-treatment of diabetic rats: effects on duodenal calcium absorption. Endocrinology 100:67–73PubMedCrossRefGoogle Scholar
  29. 29.
    Seino Y, Sierra RI, Sonn YM, Jafari A, Birge SJ, Avioli LV (1983) The duodenal 1α,25-dihydroxyvitamin D3 receptor in rats with experimentally induced diabetes. Endocrinology 113:1721–1725PubMedCrossRefGoogle Scholar
  30. 30.
    Nyomba BL, Verhaeghe J, Thomasset M, Lissens W, Bouillon R (1989) Bone mineral homeostasis in spontaneously diabetic BB rats. I. Abnormal vitamin D metabolism and impaired active intestinal calcium absorption. Endocrinology 124:565–572PubMedCrossRefGoogle Scholar
  31. 31.
    Yamamoto M (2015) Insights into bone fragility in diabetes: the crucial role of bone quality on skeletal strength. Endocr J 62:299–308PubMedCrossRefGoogle Scholar
  32. 32.
    Sealand R, Razavi C, Adler RA (2013) Diabetes mellitus and osteoporosis. Curr Diab Rep 13:411–418PubMedCrossRefGoogle Scholar
  33. 33.
    Hamilton EJ, Rakic V, Davis WA, Chubb SA, Kamber N, Prince RL, Davis TM (2009) Prevalence and predictors of osteopenia and osteoporosis in adults with type 1 diabetes. Diabet Med 26:45–52PubMedCrossRefGoogle Scholar
  34. 34.
    Saha MT, Sievänen H, Salo MK, Tulokas S, Saha HH (2009) Bone mass and structure in adolescents with type 1 diabetes compared to healthy peers. Osteoporos Int 20:1401–1406PubMedCrossRefGoogle Scholar
  35. 35.
    Lumachi F, Camozzi V, Tombolan V, Luisetto G (2009) Bone mineral density, osteocalcin, and bone-specific alkaline phosphatase in patients with insulin-dependent diabetes mellitus. Ann N Y Acad Sci 1173(Suppl 1):E64–E67PubMedCrossRefGoogle Scholar
  36. 36.
    Yaturu S, Humphrey S, Landry C, Jain SK (2009) Decreased bone mineral density in men with metabolic syndrome alone and with type 2 diabetes. Med Sci Monit 15:CR5–CR9PubMedGoogle Scholar
  37. 37.
    Yamaguchi T, Kanazawa I, Yamamoto M, Kurioka S, Yamauchi M, Yano S, Sugimoto T (2009) Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes. Bone 45:174–179PubMedCrossRefGoogle Scholar
  38. 38.
    Lapmanee S, Charoenphandhu N, Aeimlapa R, Suntornsaratoon P, Wongdee K, Tiyasatkulkovit W, Kengkoom K, Chaimongkolnukul K, Seriwatanachai D, Krishnamra N (2014) High dietary cholesterol masks type 2 diabetes-induced osteopenia and changes in bone microstructure in rats. Lipids 49:975–986PubMedCrossRefGoogle Scholar
  39. 39.
    Petit MA, Paudel ML, Taylor BC, Hughes JM, Strotmeyer ES, Schwartz AV, Cauley JA, Zmuda JM, Hoffman AR, Ensrud KE, Osteoporotic Fractures in Men Study Group (2010) Bone mass and strength in older men with type 2 diabetes: the osteoporotic fractures in men study. J Bone Miner Res 25:285–291PubMedCrossRefGoogle Scholar
  40. 40.
    Farr JN, Drake MT, Amin S, Melton LJ 3rd, McCready LK, Khosla S (2014) In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res 29:787–795PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Patsch JM, Burghardt AJ, Yap SP, Baum T, Schwartz AV, Joseph GB, Link TM (2013) Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res 28:313–324PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    To WW, Wong MW (2008) Bone mineral density changes in gestational diabetic pregnancies-a longitudinal study using quantitative ultrasound measurements of the os calcis. Gynecol Endocrinol 24:519–525PubMedCrossRefGoogle Scholar
  43. 43.
    Wang W, Zhang X, Zheng J, Yang J (2010) High glucose stimulates adipogenic and inhibits osteogenic differentiation in MG-63 cells through cAMP/protein kinase A/extracellular signal-regulated kinase pathway. Mol Cell Biochem 338:115–122PubMedCrossRefGoogle Scholar
  44. 44.
    Villarino ME, Sánchez LM, Bozal CB, Ubios AM (2006) Influence of short-term diabetes on osteocytic lacunae of alveolar bone. A histomorphometric study. Acta Odontol Latinoam 19:23–28PubMedGoogle Scholar
  45. 45.
    Zhang Y, Yang JH (2013) Activation of the PI3 K/Akt pathway by oxidative stress mediates high glucose-induced increase of adipogenic differentiation in primary rat osteoblasts. J Cell Biochem 114:2595–2602PubMedCrossRefGoogle Scholar
  46. 46.
    Botolin S, Faugere MC, Malluche H, Orth M, Meyer R, McCabe LR (2005) Increased bone adiposity and peroxisomal proliferator-activated receptor-γ2 expression in type I diabetic mice. Endocrinology 146:3622–3631PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Hamann C, Goettsch C, Mettelsiefen J, Henkenjohann V, Rauner M, Hempel U, Bernhardt R, Fratzl-Zelman N, Roschger P, Rammelt S, Günther KP, Hofbauer LC (2011) Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function. Am J Physiol Endocrinol Metab 301:E1220–E1228PubMedCrossRefGoogle Scholar
  48. 48.
    Kayal RA, Tsatsas D, Bauer MA, Allen B, Al-Sebaei MO, Kakar S, Leone CW, Morgan EF, Gerstenfeld LC, Einhorn TA, Graves DT (2007) Diminished bone formation during diabetic fracture healing is related to the premature resorption of cartilage associated with increased osteoclast activity. J Bone Miner Res 22:560–568PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Burghardt AJ, Issever AS, Schwartz AV, Davis KA, Masharani U, Majumdar S, Link TM (2010) High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 95:5045–5055PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Aoki C, Uto K, Honda K, Kato Y, Oda H (2013) Advanced glycation end products suppress lysyl oxidase and induce bone collagen degradation in a rat model of renal osteodystrophy. Lab Invest 93:1170–1183PubMedCrossRefGoogle Scholar
  51. 51.
    Weinberg E, Maymon T, Weinreb M (2014) AGEs induce caspase-mediated apoptosis of rat BMSCs via TNFα production and oxidative stress. J Mol Endocrinol 52:67–76PubMedCrossRefGoogle Scholar
  52. 52.
    Kang L, Chen Q, Wang L, Gao L, Meng K, Chen J, Ferro A, Xu B (2009) Decreased mobilization of endothelial progenitor cells contributes to impaired neovascularization in diabetes. Clin Exp Pharmacol Physiol 36:e47–e56PubMedCrossRefGoogle Scholar
  53. 53.
    Hammond MA, Gallant MA, Burr DB, Wallace JM (2014) Nanoscale changes in collagen are reflected in physical and mechanical properties of bone at the microscale in diabetic rats. Bone 60:26–32PubMedCrossRefGoogle Scholar
  54. 54.
    Kierszenbaum AL, Tres LL (2012) Connective tissue. In: Kierszenbaum AL, Tres LL (eds) Histology and cell biology: an introduction to pathology, 3rd edn. Elsevier, Philadelphia, pp 111–149CrossRefGoogle Scholar
  55. 55.
    Feng YF, Wang L, Zhang Y, Li X, Ma ZS, Zou JW, Lei W, Zhang ZY (2013) Effect of reactive oxygen species overproduction on osteogenesis of porous titanium implant in the present of diabetes mellitus. Biomaterials 34:2234–2243PubMedCrossRefGoogle Scholar
  56. 56.
    McCarthy AD, Molinuevo MS, Cortizo AM (2013) Ages and bone ageing in diabetes mellitus. J Diabetes Metab 4:276Google Scholar
  57. 57.
    Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21:195–214PubMedCrossRefGoogle Scholar
  58. 58.
    Silva MJ, Brodt MD, Lynch MA, McKenzie JA, Tanouye KM, Nyman JS, Wang X (2009) Type 1 diabetes in young rats leads to progressive trabecular bone loss, cessation of cortical bone growth, and diminished whole bone strength and fatigue life. J Bone Miner Res 24:1618–1627PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Samsa WE, Zhou X, Zhou G (2016) Signaling pathways regulating cartilage growth plate formation and activity. Semin Cell Dev Biol. doi: 10.1016/j.semcdb.2016.07.008 (in press) CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Wu S, Aguilar AL, Ostrow V, De Luca F (2011) Insulin resistance secondary to a high-fat diet stimulates longitudinal bone growth and growth plate chondrogenesis in mice. Endocrinology 152:468–475PubMedCrossRefGoogle Scholar
  61. 61.
    Yakar S, Isaksson O (2016) Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis: lessons from mouse models. Growth Horm IGF Res 28:26–42PubMedCrossRefGoogle Scholar
  62. 62.
    Mackie EJ, Ahmed YA, Tatarczuch L, Chen KS, Mirams M (2008) Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol 40:46–62PubMedCrossRefGoogle Scholar
  63. 63.
    Yao Y, Zhai Z, Wang Y (2014) Evaluation of insulin medium or chondrogenic medium on proliferation and chondrogenesis of ATDC5 cells. Biomed Res Int 2014:569241PubMedPubMedCentralGoogle Scholar
  64. 64.
    Lebl J, Schober E, Zidek T, Baldis S, Rami B, Pruhova S, Kolouskova S, Snajderova M, Frisch H (2003) Growth data in large series of 587 children and adolescents with type 1 diabetes mellitus. Endocr Regul 37:153–161PubMedGoogle Scholar
  65. 65.
    Armas LA, Akhter MP, Drincic A, Recker RR (2012) trabe-cular bone histomorphometry in humans with type 1 diabetes mellitus. Bone 50:91–96PubMedCrossRefGoogle Scholar
  66. 66.
    Muñoz MT, Barrios V, Pozo J, Argente J (1996) Insulin-like growth factor I, its binding proteins 1 and 3, and growth hormone-binding protein in children and adolescents with insulin-dependent diabetes mellitus: clinical implications. Pediatr Res 39:992–998PubMedCrossRefGoogle Scholar
  67. 67.
    Edge JA, Dunger DB, Matthews DR, Gilbert JP, Smith CP (1990) Increased overnight growth hormone concentrations in diabetic compared with normal adolescents. J Clin Endocrinol Metab 71:1356–1362PubMedCrossRefGoogle Scholar
  68. 68.
    Aeimlapa R, Wongdee K, Charoenphandhu N, Suntornsaratoon P, Krishnamra N (2014) Premature chondrocyte apoptosis and compensatory upregulation of chondroregulatory protein expression in the growth plate of Goto-Kakizaki diabetic rats. Biochem Biophys Res Commun 452:395–401PubMedCrossRefGoogle Scholar
  69. 69.
    Wongdee K, Krishnamra N, Charoenphandhu N (2012) Endochondral bone growth, bone calcium accretion, and bone mineral density: how are they related? J Physiol Sci 62:299–307PubMedCrossRefGoogle Scholar
  70. 70.
    Hough S, Avioli LV, Bergfeld MA, Fallon MD, Slatopolsky E, Teitelbaum SL (1981) Correction of abnormal bone and mineral metabolism in chronic streptozotocin-induced diabetes mellitus in the rat by insulin therapy. Endocrinology 108:2228–2234PubMedCrossRefGoogle Scholar
  71. 71.
    Bain S, Ramamurthy NS, Impeduglia T, Scolman S, Golub LM, Rubin C (1997) Tetracycline prevents cancellous bone loss and maintains near-normal rates of bone formation in streptozotocin diabetic rats. Bone 21:147–153PubMedCrossRefGoogle Scholar
  72. 72.
    Raskin P, Stevenson MR, Barilla DE, Pak CY (1978) The hypercalciuria of diabetes mellitus: its amelioration with insulin. Clin Endocrinol (Oxf) 9:329–335CrossRefGoogle Scholar
  73. 73.
    Anwana AB, Garland HO (1990) Renal calcium and magnesium handling in experimental diabetes mellitus in the rat. Acta Endocrinol (Copenh) 122:479–486CrossRefGoogle Scholar
  74. 74.
    Garland HO, Forshaw AG, Sibley CP (1997) Dietary essential fatty acid supplementation, urinary calcium excretion and reproductive performance in the diabetic pregnant rat. J Endocrinol 153:357–363PubMedCrossRefGoogle Scholar
  75. 75.
    Huang CQ, Ma GZ, Tao MD, Ma XL, Liu QX, Feng J (2009) The relationship among renal injury, changed activity of renal 1-α hydroxylase and bone loss in elderly rats with insulin resistance or type 2 diabetes mellitus. J Endocrinol Invest 32:196–201PubMedCrossRefGoogle Scholar
  76. 76.
    Singh HJ, Garland HO (1989) A comparison of the effects of oral and intravenous glucose administration on renal calcium excretion in the rat. Q J Exp Physiol 74:531–540PubMedCrossRefGoogle Scholar
  77. 77.
    Birdsey TJ, Husain SM, Garland HO, Sibley CP (1995) The effect of diabetes mellitus on urinary calcium excretion in pregnant rats and their offspring. J Endocrinol 145:11–18PubMedCrossRefGoogle Scholar
  78. 78.
    Verhaeghe J, Bouillon R, Nyomba BL, Lissens W, Van Assche FA (1986) Vitamin D and bone mineral homeostasis during pregnancy in the diabetic BB rat. Endocrinology 118:1019–1025PubMedCrossRefGoogle Scholar
  79. 79.
    Kashef S, Karamizadeh Z (2002) Hypercalciuria, hyperphosphaturia and growth retardation in children with diabetes mellitus. Iran J Med Sci 27:11–14Google Scholar
  80. 80.
    Lee CT, Lien YH, Lai LW, Chen JB, Lin CR, Chen HC (2006) Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus. Kidney Int 69:1786–1791PubMedCrossRefGoogle Scholar
  81. 81.
    Mandon B, Siga E, Chabardes D, Firsov D, Roinel N, De Rouffignac C (1993) Insulin stimulates Na+, Cl, Ca2+, and Mg2+ transports in TAL of mouse nephron: cross-potentiation with AVP. Am J Physiol 265:F361–F369PubMedGoogle Scholar
  82. 82.
    Gollaher CJ, Wood RJ, Holl M, Allen LH (1984) A comparison of amino acid-induced hypercalciuria in sham-operated and parathyroidectomized rats. J Nutr 114:622–626PubMedCrossRefGoogle Scholar
  83. 83.
    Wongsurawat N, Armbrecht HJ (1985) Insulin modulates the stimulation of renal 1,25-dihydroxyvitamin D3 production by parathyroid hormone. Acta Endocrinol (Copenh) 109:243–248CrossRefGoogle Scholar
  84. 84.
    Anderson RL, Ternes SB, Strand KA, Rowling MJ (2010) Vitamin D homeostasis is compromised due to increased urinary excretion of the 25-hydroxycholecalciferol-vitamin D-binding protein complex in the Zucker diabetic fatty rat. Am J Physiol Endocrinol Metab 299:E959–E967PubMedCrossRefGoogle Scholar
  85. 85.
    David V, Dai B, Martin A, Huang J, Han X, Quarles LD (2013) Calcium regulates FGF-23 expression in bone. Endocrinology 154:4469–4482PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Andrukhova O, Smorodchenko A, Egerbacher M, Streicher C, Zeitz U, Goetz R, Shalhoub V, Mohammadi M, Pohl EE, Lanske B, Erben RG (2014) FGF23 promotes renal calcium reabsorption through the TRPV5 channel. EMBO J 33:229–246PubMedPubMedCentralGoogle Scholar
  87. 87.
    Wolf MT, An SW, Nie M, Bal MS, Huang CL (2014) Klotho up-regulates renal calcium channel transient receptor potential vanilloid 5 (TRPV5) by intra- and extracellular N-glycosylation-dependent mechanisms. J Biol Chem 289:35849–35857PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Chen CD, Podvin S, Gillespie E, Leeman SE, Abraham CR (2007) Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci USA 104:19796–19801PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Fajol A, Chen H, Umbach AT, Quarles LD, Lang F, Föller M (2016) Enhanced FGF23 production in mice expressing PI3K-insensitive GSK3 is normalized by β-blocker treatment. FASEB J 30:994–1001PubMedCrossRefGoogle Scholar
  90. 90.
    Teerapornpuntakit J, Wongdee K, Krishnamra N, Charoenphandhu N (2016) Expression of osteoclastogenic factor transcripts in osteoblast-like UMR-106 cells after exposure to FGF-23 or FGF-23 combined with parathyroid hormone. Cell Biol Int 40:329–340PubMedCrossRefGoogle Scholar
  91. 91.
    Wolf M (2012) Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int 82:737–747PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Nellans HN, Goldsmith RS (1981) Transepithelial calcium transport by rat cecum: high-efficiency absorptive site. Am J Physiol 240:G424–G431PubMedGoogle Scholar
  93. 93.
    Karbach U, Feldmeier H (1993) The cecum is the site with the highest calcium absorption in rat intestine. Dig Dis Sci 38:1815–1824PubMedCrossRefGoogle Scholar
  94. 94.
    Charoenphandhu N, Suntornsaratoon P, Jongwattanapisan P, Wongdee K, Krishnamra N (2012) Enhanced trabecular bone resorption and microstructural bone changes in rats after removal of the cecum. Am J Physiol Endocrinol Metab 303:E1069–E1075PubMedCrossRefGoogle Scholar
  95. 95.
    Jongwattanapisan P, Suntornsaratoon P, Wongdee K, Dorkkam N, Krishnamra N, Charoenphandhu N (2012) Impaired body calcium metabolism with low bone density and compensatory colonic calcium absorption in cecectomized rats. Am J Physiol Endocrinol Metab 302:E852–E863PubMedCrossRefGoogle Scholar
  96. 96.
    Yirmiya R, Goshen I, Bajayo A, Kreisel T, Feldman S, Tam J, Trembovler V, Csernus V, Shohami E, Bab I (2006) Depression induces bone loss through stimulation of the sympathetic nervous system. Proc Natl Acad Sci USA 103:16876–16881PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Huang HH, Brennan TC, Muir MM, Mason RS (2009) Functional α1- and β2-adrenergic receptors in human osteoblasts. J Cell Physiol 220:267–275PubMedCrossRefGoogle Scholar
  98. 98.
    Nuntapornsak A, Wongdee K, Thongbunchoo J, Krishnamra N, Charoenphandhu N (2010) Changes in the mRNA expression of osteoblast-related genes in response to β3-adrenergic agonist in UMR106 cells. Cell Biochem Funct 28:45–51PubMedCrossRefGoogle Scholar
  99. 99.
    Charoenphandhu N, Suntornsaratoon P, Krishnamra N, Sa-Nguanmoo P, Tanajak P, Wang X, Liang G, Li X, Jiang C, Chattipakorn N, Chattipakorn S (2016) Fibroblast growth factor-21 restores insulin sensitivity but induces aberrant bone microstructure in obese insulin-resistant rats. J Bone Miner Metab. doi: 10.1007/s00774-016-0745-z (in press) PubMedCrossRefGoogle Scholar
  100. 100.
    Palermo A, D’Onofrio L, Eastell R, Schwartz AV, Pozzilli P, Napoli N (2015) Oral anti-diabetic drugs and fracture risk, cut to the bone: safe or dangerous? A narrative review. Osteoporos Int 26:2073–2089PubMedCrossRefGoogle Scholar
  101. 101.
    Tsentidis C, Gourgiotis D, Kossiva L, Doulgeraki A, Marmarinos A, Galli-Tsinopoulou A, Karavanaki K (2016) Higher levels of s-RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis. Osteoporos Int 27:1631–1643PubMedCrossRefGoogle Scholar
  102. 102.
    Won HY, Lee JA, Park ZS, Song JS, Kim HY, Jang SM, Yoo SE, Rhee Y, Hwang ES, Bae MA (2011) Prominent bone loss mediated by RANKL and IL-17 produced by CD4+ T cells in TallyHo/JngJ mice. PLoS ONE 6:e18168PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Motyl KJ, Botolin S, Irwin R, Appledorn DM, Kadakia T, Amalfitano A, Schwartz RC, McCabe LR (2009) Bone inflammation and altered gene expression with type I diabetes early onset. J Cell Physiol 218:575–583PubMedCrossRefGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan 2016

Authors and Affiliations

  • Kannikar Wongdee
    • 1
    • 3
  • Nateetip Krishnamra
    • 1
    • 2
  • Narattaphol Charoenphandhu
    • 1
    • 2
    Email author
  1. 1.Center of Calcium and Bone Research (COCAB), Faculty of ScienceMahidol UniversityBangkokThailand
  2. 2.Department of Physiology, Faculty of ScienceMahidol UniversityBangkokThailand
  3. 3.Faculty of Allied Health SciencesBurapha UniversityChonburiThailand

Personalised recommendations