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Regucalcin and metabolic disorders: osteoporosis and hyperlipidemia are induced in regucalcin transgenic rats

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Regucalcin transgenic (TG) rat has been generated to determine the role in metabolic disorders. Regucalcin homozygote male and female rats induce a prominent increase in regucalcin protein in the various tissues. Bone loss has been found to induce in regucalcin TG rats with growing (5 weeks old) and aging (50 weeks old). Osteoclastogenesis has been shown to stimulate in culture with the bone marrow cells obtained from regucalcin TG rats. Exogenous regucalcin stimulates osteoclastogenesis in mouse marrow culture in vitro. Regucalcin has a suppressive effect on the differentiation and mineralization in osteoblastic MC3T3-E1 cells in vitro. The mechanism by which regucalcin TG rat induces bone loss may result from the enhancement of osteoclastic bone resorption and the suppression of osteoblastic bone formation. Moreover, regucalcin TG rat has been found to induce hyperlipidemia with increasing age (14–50 weeks); serum triglyceride, high-density lipoprotein (HDL)-cholesterol, free fatty acid, albumin and calcium concentrations are markedly increased in regucalcin TG male and female rats with increasing age. The decrease in lipid and glycogen contents in liver tissues is induced in regucalcin TG rats. The gene expression of leptin and adiponectin is suppressed in the TG rats. Overexpression of regucalcin has been shown to enhance glucose utilization and lipid production in the cloned rat hepatoma H4-II-E cells in vitro, and insulin resistance is seen in the cells. The expression of glucose transporter 2 mRNA is increased in the transfectants, while it has been shown to suppress insulin receptor and phosphatidylinositol 3-kinase mRNA expressions that are involved in insulin signaling. This review proposes that regucalcin relates in osteoporosis and hyperlipidemia, and that the regucalcin TG rat model may be useful in determining the pathophysiologic state and the development of therapeutic tool for osteoporosis and hyperlipidemia.

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References

  1. Cheung WY (1980) Calmodulin plays a pivotal role in cellular regulation. Science 202:19–27

    Article  Google Scholar 

  2. Nishizuka Y (1986) Studies and perspectives of protein kinase C. Science 233:305–312

    Article  CAS  PubMed  Google Scholar 

  3. Kraus-Friedman N, Feng L (1996) The role of intracellular Ca2+ in the regulation of gluconeogenesis. Metabolism 42:389–403

    Article  Google Scholar 

  4. Yamaguchi M, Yamamoto T (1978) Purification of calcium binding substance from soluble fraction of normal rat liver. Chem Pharm Bull 26:1915–1918

    CAS  PubMed  Google Scholar 

  5. Yamaguchi M, Sugii K (1981) Properties of calcium-binding protein isolated from the soluble fraction of normal rat liver. Chem Pharm Bull 29:567–570

    CAS  PubMed  Google Scholar 

  6. Yamaguchi M (1988) Physicochemical properties of calcium-binding protein isolated from rat liver cytosol: Ca2+-induced conformational changes. Chem Pharm Bull 36:286–290

    CAS  PubMed  Google Scholar 

  7. Shimokawa N, Yamaguchi M (1993) Molecular cloning and sequencing of the cDNA coding for a calcium-binding protein regucalcin from rat liver. FEBS Lett 327:251–255

    Article  CAS  PubMed  Google Scholar 

  8. Yamaguchi M, Yoshida H (1985) Regulatory effect of calcium-binding protein isolated from rat liver cytosol on activation of fructose 1, 6-diphosphatase by Ca2+-calmodulin. Chem Pharm Bull 33:4489–4493

    CAS  PubMed  Google Scholar 

  9. Yamaguchi M, Shibano H (1987) Calcium-binding protein isolated from rat liver cytosol reverses activation of pyruvate kinase by Ca2+. Chem Pharm Bull 35:2025–2029

    CAS  PubMed  Google Scholar 

  10. Yamaguchi M, Shibano H (1987) Effect of calcium-binding protein on the activation of phosphorylase a in rat hepatic particulate glycogen by Ca2+. Chem Pharm Bull 35:2581–2584

    CAS  PubMed  Google Scholar 

  11. Yamaguchi M, Shibano H (1987) Reversible effect of calcium-binding protein on the Ca2+-induced activation of succinate dehydrogenase in rat liver mitochondria. Chem Pharm Bull 35:3766–3770

    CAS  PubMed  Google Scholar 

  12. Yamaguchi M, Mori S (1988) Effect of Ca2+ and Zn2+ on 5′-nucleotidase activity in rat liver plasma membranes: hepatic calcium-binding protein (regucalcin) reverses the Ca2+ effect. Chem Pharm Bull 36:321–325

    CAS  PubMed  Google Scholar 

  13. Fujita T, Uchida K, Maruyama N (1992) Purification of senescence marker protein-30 (SMP30) and its androgen-independent decrease with age in the rat liver. Biochim Biophys Acta 1116:122–128

    CAS  PubMed  Google Scholar 

  14. Fujita T, Shirasawa T, Uchida K, Maruyama N (1992) Isolation of cDNA clone encoding rat senescence marker protein-30 (SMP30) and its tissue distribution. Biochim Biophys Acta 1132:297–305

    CAS  PubMed  Google Scholar 

  15. Yamaguchi M (1992) A novel Ca2+-binding protein regucalcin and calcium inhibition. Regulatory role in liver cell function. In: Kohama K (ed) Calcium inhibition. Japan Sci Soc Press/CRC Press, Tokyo/Boca Raton, pp 19–41

    Google Scholar 

  16. Yamaguchi M (1998) Role of calcium-binding protein regucalcin in regenerating rat liver. J Gastroentrol Hepatol 13(Suppl):S106–S112

    CAS  Google Scholar 

  17. Yamaguchi M (2000) Role of regucalcin in calcium signaling. Life Sci 66:1769–1780

    Article  CAS  PubMed  Google Scholar 

  18. Yamaguchi M (2000) The role of regucalcin in nuclear regulation of regenerating liver. Biochem Biophys Res Commun 276:1–6

    Google Scholar 

  19. Yamaguchi M (2002) Impact of aging on calcium channels and pumps. In: Mattson MP (ed) Calcium homeostasis and signaling in aging. Elsevier, Amsterdam, pp 47–65

    Chapter  Google Scholar 

  20. Yamaguchi M (2005) Role of regucalcin in maintaining cell homeostasis and function. Int J Mol Med 15:372–389

    Google Scholar 

  21. Misawa H, Yamaguchi M (2000) The gene of Ca2+-binding protein regucalcin is highly conserved in vertebrate species. Int J Mol Med 6:191–196

    CAS  PubMed  Google Scholar 

  22. Nikapitiya C, De Zoysa M, Kang HS, Oh C, Whang I, Lee J (2008) Molecular characterization and expression analysis of regucalcin in disk abalone (Haliotis discus discus): intramuscular calcium administration stimulates the regucalcin mRNA expression. Comp Biochem Physiol B Biochem Mol Biol 150:117–124

    Article  PubMed  Google Scholar 

  23. Shimokawa N, Matsuda Y, Yamaguchi M (1995) Genomic cloning and chromosomal assignment of rat regucalcin gene. Mol Cell Biochem 151:157–163

    Article  CAS  PubMed  Google Scholar 

  24. Thiselton DL, McDowall J, Brandau O, Ramser J, d’Esposito F, Bhattacharga SS, Ross MT, Hardcastle AJ, Meindl A (2002) An integrated, functionally annotated gene map of the DXS8026-ELK1 internal on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders. Genomics 79:560–572

    Article  CAS  PubMed  Google Scholar 

  25. Yamaguchi M, Makino R, Shimokawa N (1996) The 5′end seguences and exon organization in rat regucalcin gene. Mol Cell Biochem 165:145–150

    Article  CAS  PubMed  Google Scholar 

  26. Murata T, Yamaguchi M (1998) Ca2+ administration stimulates the binding of AP-1 factor to the 5′-flanking region of the rat gene for the Ca2+-binding protein regucalcin. Biochem J 329:157–163

    CAS  PubMed  Google Scholar 

  27. Miasawa H, Yamaguchi M (2000) Involvement of hepatic nuclear factor I binding motif in transcriptional regulation of Ca2+-binding protein regucalcin gene. Biochem Biophys Res Commun 269:270–278

    Article  Google Scholar 

  28. Misawa H, Yamaguchi M (2002) Indentification of transcription factor in the promoter region of rat regucalcin gene: binding of nuclear factor I-A1 to TTGGC motif. J Cell Biochem 84:795–802

    Article  PubMed  Google Scholar 

  29. Misawa H, Yamaguchi M (2001) Molecular cloning and sequencing of the cDNA coding for a novel regucalcin gene promoter region-related protein in rat, mouse and human liver. Int J Mol Med 8:513–520

    CAS  PubMed  Google Scholar 

  30. Sawada N, Yamaguchi M (2005) A novel regucalcin gene promoter region-related protein: comparison of nucleotide and amino acid sequnces in vertebrates species. Int J Mol Med 15:97–104

    CAS  PubMed  Google Scholar 

  31. Yamaguchi M (2009) Novel protein RGPR-p117: its role as the regucalcin gene transcription factor. Mol Cell Biochem 327:53–63

    Article  CAS  PubMed  Google Scholar 

  32. Nejak-Bowen KN, Zeng G, Tan X, Cieply B, Monga SP (2009) Beta-catenin regulates vitamin C biosynthesis and cell survival in murine liver. J Biol Chem 284:28115–28127

    Article  CAS  PubMed  Google Scholar 

  33. Murata T, Yamaguchi M (1999) Promoter characterization of the rat gene for Ca2+-binding protein regucalcin. Transcriptional regulation by signaling factors. J Biol Chem 274:1277–1285

    Article  CAS  PubMed  Google Scholar 

  34. Misawa H, Yamaguchi M (2000) Intracellular signaling factors-enhanced hepatic nuclear protein binding to TTGGC sequence in the rat regucalcin gene promoter: involvement of protein phosphorylation. Biochem Biophys Res Commun 279:275–281

    Article  CAS  PubMed  Google Scholar 

  35. Misawa H, Yamaguchi M (2002) Gene expression for a novel protein RGPR-p117 in various species: the stimulation by intracellular signaling factors. J Cell Biochem 87:188–193

    Article  CAS  PubMed  Google Scholar 

  36. Sawada N, Yamaguchi M (2006) Overexpression of RGPR-p117 enhances regucalcin gene promoter activity in cloned normal rat kidney proximal tubular epithelial cells: involvement of TTGGC motif. J Cell Biochem 99:589–597

    Article  CAS  PubMed  Google Scholar 

  37. Yamaguchi M, Nakajima M (1999) Involvement of intracellular signaling factors in the serum-enhanced Ca2+-binding protein regucalcin mRNA expression in the cloned rat hepatoma cells (H4-II-E). J Cell Biochem 74:81–89

    Article  CAS  PubMed  Google Scholar 

  38. Nakagawa T, Yamaguchi M (2005) Hormonal regulation on regucalcin mRNA expression in cloned normal rat kidney proximal tubular epithelial NRK52E cells. J Cell Biochem 95:589–597

    Article  CAS  PubMed  Google Scholar 

  39. Yamaguchi M, Isogai M (1993) Tissue concentration of calcium-binding protein regucalcin in rats by enzyme-linked immunoadsorbent assay. Mol Cell Biochem 122:65–68

    Article  CAS  PubMed  Google Scholar 

  40. Shimokawa N, Isogai M, Yamaguchi M (1995) Specific species and tissue differences for the gene expression of calcium-binding protein regucalcin. Mol Cell Biochem 143:67–71

    Article  CAS  PubMed  Google Scholar 

  41. Shimokawa N, Yamaguchi M (1992) Calcium administration stimulates the expression of calcium-binding protein regucalcin mRNA in rat liver. FEBS Lett 305:151–154

    Article  CAS  PubMed  Google Scholar 

  42. Yamaguchi M, Hamano T, Misawa H (2000) Expression of Ca2+-binding protein regucalcin in rat brain neurons: inhibitory effect on protein phosphatase activity. Brain Res Bull 52:343–348

    Article  CAS  PubMed  Google Scholar 

  43. Yamaguchi M, Nakajima R (2002) Role of regucalcin as an activator of sarcoplasmic reticulum Ca2+-ATPase activity in rat heart muscle. J Cell Biochem 86:184–193

    Article  CAS  PubMed  Google Scholar 

  44. Yamaguchi M, Misawa H, Uchiyama S, Morooka Y, Tsurusaki Y (2002) Role of endogenous regucalcin in bone metabolism: bone loss is induced in regucalcin transgenic rats. Int J Mol Med 10:377–383

    CAS  PubMed  Google Scholar 

  45. Maia CJ, Santos CR, Schmitt F, Socorro S (2008) Regucalcin is expressed in rat mammary gland and prostate and down-regulated by 17beta-estradiol. Mol Cell Biochem 311:81–86

    Article  CAS  PubMed  Google Scholar 

  46. Maia CJ, Santos CR, Schmitt F, Socorro S (2009) Regucalcin is under-expressed in human breast and prostate cancers: effect of sex steroid hormones. J Cell Biochem 107:667–676

    Article  CAS  PubMed  Google Scholar 

  47. Murata T, Shinya N, Yamaguchi M (1997) Expression of calcium-binding protein regucalcin mRNA in the cloned human hepatoma cells (HepG2): stimulation by insulin. Mol Cell Biochem 175:163–168

    Article  CAS  PubMed  Google Scholar 

  48. Yamaguchi M, Oishi K (1995) 17β-Estradiol stimulates the expression of hepatic calcium-binding protein regucalcin mRNA in rats. Mol Cell Biochem 143:137–141

    Article  CAS  PubMed  Google Scholar 

  49. Kondo Y, Inai Y, Sato Y, Handa S, Kubo S, Shimokado K, Goto S, Nishikimi M, Maruyama N, Ishigami A (2006) Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy. Proc Natl Acad Sci USA 103:5723–5728

    Article  CAS  PubMed  Google Scholar 

  50. Yamaguchi M, Morooka Y, Misawa H, Tsurusaki Y, Nakajima R (2002) Role of endogenous regucalcin in transgenic rats: suppression of kidney cortex cytosolic protein phosphatase activity and enhancement of heart muscle microsomal Ca2+-ATPase activity. J Cell Biochem 86:520–529

    Article  CAS  PubMed  Google Scholar 

  51. Morooka Y, Yamaguchi M (2001) Suppressive role of endogenous regucalcin in the regulation of protein phosphatase activity in rat renal cortex cytosol. J Cell Biochem 81:639–646

    Article  CAS  PubMed  Google Scholar 

  52. Hunter T (1995) Protein kinases and phosphatases: the Yin and Yang of protein phosphorylation and signaling. Cell 80:225–236

    Article  CAS  PubMed  Google Scholar 

  53. Yamaguchi M, Igarashi A, Uchiyama S, Sawada N (2004) Hyperlipidemia is induced in regucalcin transgenic rats with increasing age. Int J Mol Med 14:647–651

    CAS  PubMed  Google Scholar 

  54. Majeska RJ, Wuthier RE (1975) Studies on matrix vesicles isolated from chick epiphyseal cartilage. Association of pyrophosphatase and ATPase activities with alkaline phosphatase. Biochim Biophys Acta 391:51–60

    CAS  PubMed  Google Scholar 

  55. Lian JB, Stein GS, Cannalis E, Roky PG, Boskey AL (1999) Bone formation: osteoblast lineage cells, growth factor, matrix protein, and the mineralization process. In: Favus MJ (ed) Primer on the metabolic bone disease and disorders of mineral metabolism, 4th edn. Lippincott Williams & Wilkins Press, New York, pp 14–29

    Google Scholar 

  56. Cooper C, Melton J III (1992) Epidemiology of osteoporosis. Trends Endocrinol Metab 3:224–229

    Article  CAS  PubMed  Google Scholar 

  57. Weitzmann MN, Pacifici R (2006) Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 116:1186–1194

    Article  CAS  PubMed  Google Scholar 

  58. Zaidi M, Blair HC, Moonga BS, Abe E, Huang CL-H (2003) Osteoclastgenesis, bone resorption, and osteoclast-based therapeutics. J Bone Miner Res 18:599–609

    Article  PubMed  Google Scholar 

  59. Yamaguchi M, Sawada N, Uchiyama S, Misawa H, Ma ZJ (2004) Expression of regucalcin in rat bone marrow cells: involvement of osteoclastic bone resorption in regucalcin transgenic rats. Int J Mol Med 13:437–443

    CAS  PubMed  Google Scholar 

  60. Uchiyama S, Yamaguchi M (2004) Bone loss in regucalcin transgenic rats: enhancement of osteoclastic cell formation from bone marrow of rats with increasing age. Int J Mol Med 14:451–455

    CAS  PubMed  Google Scholar 

  61. Tanaka S, Nakamura I, Inoue J-I, Oda H, Nakamura K (2003) Signal transduction pathways regulating osteoclast differentiation and function. J Bone Miner Metab 21:123–133

    Article  PubMed  Google Scholar 

  62. Yamaguchi M, Uchiyama S (2005) Regucalcin stimulates osteoclast-like cell formation in mouse marrow cultures. J Cell Biochem 94:794–803

    Article  CAS  PubMed  Google Scholar 

  63. Zou W, Hakim I, Tschoep K, Endres A, Bar-Shavit Z (2001) Tumor necrosis factor-α mediates RANK ligand stimulation of osteoclast-differentiation by an autocrine mechanism. J Cell Biochem 83:70–83

    Article  CAS  PubMed  Google Scholar 

  64. Yamaguchi M, Kobayashi M, Uchiyama S (2005) Suppressive effect of regucalcin on cell differentiation and mineralization in osteoblastic MC3T3-E1 cells. J Cell Biochem 96:543–554

    Article  CAS  PubMed  Google Scholar 

  65. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764

    Article  CAS  PubMed  Google Scholar 

  66. Lee MH, Kim YJ, Kim HJ, Park HD, Kang AR, Kyung HM, Sung IM, Wozney JM, Kim HJ, Ryoo HM (2003) BKP-2-induced Runx2 expression is mediated by Dlx5, and TGF-beta 1 opposes the BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression. J Biol Chem 278:34387–34394

    Article  CAS  PubMed  Google Scholar 

  67. Lowenstein CJ, Dinerman JL, Synder SH (1994) Nitric oxide: a physiologic messenger. Ann Intern Med 120:227–237

    CAS  PubMed  Google Scholar 

  68. Otomo Y, Yamaguchi M (2006) Regulatory effect of exogenous regucalcin on cell function in osteoblastic MC3T3-E1 cells: involvement of intracellular signaling factor. Int J Mol Med 18:321–327

    CAS  PubMed  Google Scholar 

  69. Yamaguchi M, Mori S, Kato S (1988) Calcium-binding protein regucalcin is an activator (Ca2+-Mg2+)-adenosine triphosphatase in the plasma membranes of rat liver. Chem Pharm Bull 36:3532–3539

    CAS  PubMed  Google Scholar 

  70. Centrella M, McCarthy TL, Canalis E (1990) Receptors for insulin-like growth factors-I and -II in osteoblast-enriched cultures from fetal rat bone. Endocrinology 126:39–44

    Article  CAS  PubMed  Google Scholar 

  71. Stock M, Schafer H, Fliegauf M, Otto F (2004) Identification of novel target of the bone-specific transcription factor Runx2. J Bone Miner Res 19:959–972

    Article  CAS  PubMed  Google Scholar 

  72. Yohay DA, Zhang J, Thrailkill KM, Arthur JM, Quarles LD (1994) Role of serum in the developmental expression of alkaline phosphatase in MC3T3-E1 osteoblasts. J Cell Physiol 158:467–475

    Article  CAS  PubMed  Google Scholar 

  73. Yamaguchi M, Otomo Y, Uchiyama S, Nakagawa T (2008) Hormonal regulation of regucalcin mRNA expression in osteoblastic MC3T3-E1 cells. Int J Mol Med 21:771–775

    CAS  PubMed  Google Scholar 

  74. Asagiri M, Takayanagi H (2007) The molecular understanding of osteoclast differentiation. Bone 40:251–264

    Article  CAS  PubMed  Google Scholar 

  75. Jilka RL (2007) Molecular and cellular mechanism of the anabolic effect of intermittent PTH. Bone 40:1434–1446

    Article  CAS  PubMed  Google Scholar 

  76. Jotter KV, Perry MJ (2007) High-dose estrogen-induced osteogenesis is decreased in aged RUNX2 +/− mice. Bone 41:25–32

    Article  Google Scholar 

  77. Tsurusaki Y, Yamaguchi M (2003) Role of endogenous regucalcin in transgenic rats: suppression of protein tyrosine phosphatase and ribonucleic acid synthesis activities in liver nucleus. In J Mol Med 12:207–211

    CAS  Google Scholar 

  78. Ma ZJ, Yamaguchi M (2003) Regulatory effect of regucalcin on nitric oxide synthase activity in rat kidney cortex cytosol: role of endogenous regucalcin in transgenic rats. Int J Mol Med 12:201–206

    PubMed  Google Scholar 

  79. Ma ZJ, Yamaguchi M (2002) Suppressive role of endogenous regucalcin in the regulation of nitric oxide synthase activity in heart muscle cytosol of normal and regucalcin transgenic rats. Int J Mol Med 10:761–766

    CAS  PubMed  Google Scholar 

  80. Tobisawa M, Yamaguchi M (2003) Role of endogenous regucalcin in brain function: suppression of cytosolic nitric oxide synthase and nuclear protein tyrosine phosphatase activities in brain tissue of transgenic rats. In J Mol Med 12:581–585

    CAS  Google Scholar 

  81. Weinstock PH, Bisgaier CL, Aalto-Setala K, Radner H, Ramarkrishnan R, Levak-Frank S, Essenbury AD, Zechner R, Breslow JL (1995) Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase in knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes. J Clin Invest 96:2555–2568

    Article  CAS  PubMed  Google Scholar 

  82. Lichtman AH, Clinton SK, Iiyama K, Connelly PW, Libby P, Cybulsky MI (1999) Hyperlipidemia and atherosclerotic lesion development in LDL receptor-deficient mice fed defined semipurified diets with and without cholate. Arterioscler Thromb Vasc Biol 19:1938–1944

    CAS  PubMed  Google Scholar 

  83. Jong MC, Havekes LM (2000) Insights into apolipoprotein C metabolism from transgenic and gene-targeted mice. Int J Tissue React 22:59–66

    CAS  PubMed  Google Scholar 

  84. Koopmans SJ, Jong MC, Que I, Dahlmans VE, Pijl H, Radder JK, Frolich M, Havekes LM (2001) Hyperlipidemia is associated with increased insulin-mediated glucose metabolism, reduced fatty acid metabolism and normal blood pressure in transgenic mice overexpressing human apolipoprotein C1. Diabetologia 44:437–443

    Article  CAS  PubMed  Google Scholar 

  85. Yagyu H, Lutz EP, Kako Y, Marks S, Hu Y, Choi SY, Bensadoun A, Goldberg IJ (2002) Very low density lipoprotein (VLDL) receptor-deficient mice have reduced lipoprotein lipase activity mass with VLDL receptor deficiency. J Biol Chem 277:10037–10043

    Article  CAS  PubMed  Google Scholar 

  86. Chen JY, Levy-Wilson B, Goodart S, Cooper AD (2002) Mice expressing the human CYP7A1 gene in the mouse CYP7A1 knock-out background lock induction of CYP7A1 expression by cholesterol feeding and have increased hypercholesterolemia when fed a high fat diet. J Biol Chem 277:42588–42595

    Article  CAS  PubMed  Google Scholar 

  87. Fazio S, Linton MF (2001) Mouse models of hyperlipidemia and atheroscerosis. Front Biosci 6:D515–D525

    Article  CAS  PubMed  Google Scholar 

  88. Ono H, Shibano H, Katagiri H, Yahagi N, Sakoda H, Onishi Y, Anai M, Ogihara T, Fujishiro M, Viana AY, Fukushima Y, Abe M, Shojima N, Kikuchi M, Yamada N, Oka Y, Asano T (2003) Hepatic Akt activation induces marked hypoglycemia, hepatomegaly, and hypertriglyceridemia with sterol regulatory element binding protein involvement. Diabetes 52:2905–2913

    Article  CAS  PubMed  Google Scholar 

  89. Yamaguchi M, Nakagawa T (2007) Change in lipid components in the adipose and liver tissues of regucalcin transgenic rats with increasing age: suppression of leptin and adiponectin gene expression. Int J Mol Med 20:323–328

    CAS  PubMed  Google Scholar 

  90. Nakashima C, Yamaguchi M (2006) Overexpression of regucalcin enhances glucose utilization and lipid production in cloned rat hepatoma H4-II-E cells: involvement of insulin resistance. J Cell Biochem 99:1582–1592

    Article  CAS  PubMed  Google Scholar 

  91. Nakashima C, Yamaguchi M (2007) Overexpression of regucalcin suppresses gene expression of insulin siganaling-related proteins in cloned rat hepatoma H4-II-E cells: involvement of insulin resistance. Int J Mol Med 20:709–716

    CAS  PubMed  Google Scholar 

  92. Soloman SS, Buss N, Shull J, Monnier S, Majumdar G, Wu J, Gerling IC (2005) Proteome of H4-II-E (liver) cells exposed to insulin and tumor necrosis factor-α: analysis of proteins involved in insulin resistance. J Lab Clin Med 145:275–283

    Article  Google Scholar 

  93. Roni T, Lupattelli G, Mannarino E (2006) The endocrine function of adipose tissue: an uptake. Clin Endocrinol 64:255–365

    Article  Google Scholar 

  94. Dyck DJ, Heigenhauser GJ, Bruce CR (2006) The role of adipokines as regulators of skeletal muscle fatty acid metabolism and insulin sensitivity. Acta Physiol 186:5–16

    Article  CAS  Google Scholar 

  95. Guerre-Millo M (2002) Adipose tissue hormones. J Endocrinol Invest 25:855–861

    CAS  PubMed  Google Scholar 

  96. Havel PJ (2004) Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 53:5143–5151

    Article  Google Scholar 

  97. Fukaya Y, Yamaguchi M (2005) Overexpression of regucalcin suppresses cell death and apoptosis in cloned rat hepatoma H4-II-E cells induced by insulin or insulin-like growth factor-I. J Cell Biochem 96:145–154

    Article  CAS  PubMed  Google Scholar 

  98. Solomon SS, Mishra SK, Palazzolo MR, Postlethwaite AE, Seyer JM (1997) Identification of specific sites in the TNF-α molecule promoting insulin resistance in H4-II-E liver cells. J Lab Clin Med 130:139–146

    Article  CAS  PubMed  Google Scholar 

  99. Park H, Ishigami A, Shima T, Mizuno M, Maruyama N, Yamaguchi K, Mitsuyoshi H, Minami M, Yasui K, Itoh Y, Yoshikawa T, Fukui M, Hasegawa G, Nakamura N, Ohta M, Obayashi H, Okanoue T (2009) Hepatic senescence marker protein-30 is involved in the progression of nonalcoholic fatty liver disease. J Gastroenterol. doi:10.1007/s00535-009-0154-3

  100. Hasegawa G, Yamasaki M, Kadono M, Tanaka M, Asano M, Senmaru T, Kondo Y, Fukui M, Obayashi H, Maruyama N, Nakamura N, Ishigami A (2010) Senescence marker protein-30/gluconolactonase deletion worsens glucose tolerance through impairment of acute insulin secretion. Endocrinology 151:529–536

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The author was supported in part by a Grant-in-Aid for Scientific Research (C) No. 63571053, No. 02671006, No. 06672193, No. 08672522, and No.13672292 from the Ministry of Education, Science, Sports, and Culture, Japan. Also, the author was awarded the Bounty of the Yamanouchi Foundation for Research on Metabolic Disorders, 2004, Japan.

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  1. Division of Endocrinology and Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, 1305 WMRB, Atlanta, GA, 30322-0001, USA

    Masayoshi Yamaguchi

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Yamaguchi, M. Regucalcin and metabolic disorders: osteoporosis and hyperlipidemia are induced in regucalcin transgenic rats. Mol Cell Biochem 341, 119–133 (2010). https://doi.org/10.1007/s11010-010-0443-4

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