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GENOME-WIDE SEARCH FOR THE SUSCEPTIBILITY GENES FOR OBESE DIABETES IN THE DOMINICAN REPUBLIC

Research Project

Project/Area Number 15406035
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Metabolomics
Research InstitutionOITA UNIVERSITY (2004-2005)
大分医科大学 (2003)

Principal Investigator

YOSHIMATSU Hironobu  OITA UNIVERSITY, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (00166993)

Co-Investigator(Kenkyū-buntansha) HAMAGUCHI Kazuyuki  OITA UNIVERSITY, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (60180931)
TERAO Hideo  OITA UNIVERSITY, DEPARTMENT OF HEALTH SCIENCE CENTER, PROFESSOR, 保健管理センター, 教授 (10128192)
AONO Hiroshi  OITA UNIVERSITY, FACULTY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (80150936)
SAKATA Toshiie  NAKAMURA GAKUEN UNIVERSITY, PROFESSOR, 栄養科学研究部, 教授 (50037420)
HARA Masahide  OITA UNIVERSITY, FACULTY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (10244162)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2003: ¥7,300,000 (Direct Cost: ¥7,300,000)
KeywordsDominican Republic / diabetes mellitus / obesity / insulin resistance / mitochondria / Kir 6.2 / diet-induced obesity / antiotensin II receptor blocker / PC-1 / 多型 / 生活習慣病 / SNP
Research Abstract

We reported previously that people in the Dominican Republic have extremely high prevalence of PC-1 121Q allele, which is one of the susceptibility genes for type 2 diabetes. In the research theme 1, we characterized their genetic background by analyzing the nucleotide sequences of the D-loop region of human mitochondrial DNA (mtDNA). Phylogenetic analysis of mtDNA lineages including Native Americans, Africans, and Europeans enabled us to assess relative genetic contributions of the ancestral fractions to the groups in the Dominican Republic. In the obese type 2 diabetes (OD) group, the majority (64.0%) of the mtDNA lineages were from African ancestry, whereas the Native American fraction was predominant (51.5%) in the healthy group. This difference was similarly demonstrated by phylogenetic analysis. These findings may imply ethnic-specific predisposition to OD, a possible association of an unidentified factor from African ancestry with OD in the Dominican Republic.
In the research theme 2, we analyzed the Kir 6.2 gene which is related to insulin secretion from pancreatic β cells. We showed that the 23K allele is associated with the decreased level of insulin secretion and predispose to non-obese diabetes in the Dominican Republic.
In the research theme 3, we investigated the changes of obesity-related genes and the effect of an angiotensin II receptor blocker (ARB) in diet-induced obese (DIO) mice in order to analyze candidate genes for obese-diabetes. DIO mice exhibited various changes in the expression of obesity-related genes. On the other hand, ARB ameliorated the body weight gain and the disorder of gene expression in the adipose tissue and the liver. Since adiponectin, resistin and UCP1 genes are related closely to the development of obesity and related metabolic disorders, these genes are good candidate genes for obese-diabetes.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005 2004 Other

All Journal Article (16 results) Publications (5 results)

  • [Journal Article] The neuronal histamine H1 and pro-opiomelanocortin-melancortin 4 receptors independent regulation of food intake and energy expenditure.2006

    • Author(s)
      Yoshimatsu H.
    • Journal Title

      Peptides 27

      Pages: 326-332

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Leptin downregulates ghrelin levels in streptozotocin-induced diabetic mice.2005

    • Author(s)
      Tsubone T, et al.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol 289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] The role of histamine H1 receptor and H2 receptor in LPS-induced liver injury.2005

    • Author(s)
      Masaki T, et al.
    • Journal Title

      FASEB J. 19

      Pages: 1245-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Ghrelin regulates adiposity in white adipose tissue and UCP1 mRNA expression in brown adipose tissue in mice.2005

    • Author(s)
      Tsubone T, et al.
    • Journal Title

      Regul Pept. 130

      Pages: 97-103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Hypothalamic neuronal histamine modulates febrile response but not anorexia induced by lipopolysaccharide.2005

    • Author(s)
      Chiba S, et al.
    • Journal Title

      Exp Bio Med. 230

      Pages: 334-42

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Leptin downregulates ghrelin levels in streptozotocin-induced diabetic mice.2005

    • Author(s)
      Tsubone T, Masaki T, Katsuragi I, Tanaka K, Kakuma T, Yoshimatsu H.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol. 289

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of histamine H1 receptor and H2 receptor in LPS-induced liver injury.2005

    • Author(s)
      Masaki T, Chiba S, Tatsukawa H, Noguchi H, Kakuma T, Endo M, Seike M, Watanabe T, Yoshimatsu H.
    • Journal Title

      FASEB J. 19

      Pages: 1245-1252

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ghrelin regulates adiposity in white adipose tissue and UCP1 mRNA expression in brown adipose tissue in mice.2005

    • Author(s)
      Tsubone T, Masaki T, Katsuragi I, Tanaka K, Kakuma T, Yoshimatsu H.
    • Journal Title

      Regul Pept. 130

      Pages: 97-103

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypothalamic neuronal histamine modulates febrile response but not anorexia induced by lipopolysaccharide.2005

    • Author(s)
      Chiba S, Itateyama E, Oka K, Masaki T, Sakata T, Yoshimatsu H.
    • Journal Title

      Exp Biol Med. 230

      Pages: 334-342

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypothalamic neuronal histamine modulates febrile response but not anorexia induced by lipopolysaccharide.2005

    • Author(s)
      Chiba S, et al.
    • Journal Title

      Exp Biol Med. 230

      Pages: 334-342

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic and is associated with type 2 diabetes.2004

    • Author(s)
      Hamaguchi K, et al.
    • Journal Title

      J Clin Endocrinol Metab 45

      Pages: 231-231

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Genetic Background of people in the Dominican Republic with or without obese type 2 diabetes revealed by mitochondrial DNA polymorphism.2004

    • Author(s)
      Tajima A, et al.
    • Journal Title

      J Hum Genet 49

      Pages: 495-495

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic and is associated with type 2 diabetes.2004

    • Author(s)
      Hamaguchi K, Terao H, Kusuda Y, Yamashita T, Hazoury Bahles JA, Cruz LL M, Brugal V LI, Jongchong W B, Yoshimatsu H, Sakata T.
    • Journal Title

      J Clin Endocrinol Metab. 89

      Pages: 1359-1364

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Genetic background of people in the Dominican Republic with or without obese type 2 diabetes revealed by mitochondrial DNA Polymorphism.2004

    • Author(s)
      Tajima A, Hamaguchi K, Terao H, Oribe A, Perrotta VM, Baez CA, Arias JR, Yoshimatsu H, Sakata T, Horai S.
    • Journal Title

      J Hum Genet 49

      Pages: 495-499

    • NAID

      10013600348

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Genetic background of people in the Dominican Republic with or without obese type 2 diabetes revealed by mitochondrial DNA polymorphism.2004

    • Author(s)
      Tajima A, et al.
    • Journal Title

      J Hum Genet 49

      Pages: 495-495

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of hypothalamic histamine H1 receptor in the regulation of feeding rhythm and obesity.2004

    • Author(s)
      Masaki T, et al.
    • Journal Title

      Diabetes 53

      Pages: 2250-2250

    • Related Report
      2004 Annual Research Report
  • [Publications] Masaki T, et al.: "Peripheral, but not central, administration of Adiponectin reduces visceral adiposity and upregulates the expression of uncoupling protein in agouti yellow(Av/a) obese mice"Diabetes. 52. 2266-2273 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masaki T, et al.: "Chronic central leptin infusion restores hyperglycemia independently of food intake and insulin level in streptozotocin-induced diabetic rats"Endocrinology. 144. 2741-2748 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masaki T, et al.: "Neuronal histamine regulates food intake, adiposity and uncoupling Protein expression in agouti yellow (A^y/a) obese mice"Endocrinology. 144. 3547-3554 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasuda T, et al.: "Centrally administered ghrelin suppresses sympathetic nerve activity in brown adipose tissue of rats"Neuroscience Lett.. 349. 75-78 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Itateyama E., et al.: "Hypothalamic neuronal histamine in genetically obese animals : its implication of leptin action in the brain"Exp.Biol.Med.. 228. 1132-1137 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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