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The etiological importance of reduced B-cell masses for the development of type 2 diabetes mellitus.

Research Project

Project/Area Number 09671061
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionThe University of Tokushima

Principal Investigator

SHIMA Kenji  The University of Tokushima School of Medicine, Professor, 医学部, 教授 (90028407)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Takashi  The University of Tokushima, School of Medicine, Instructor, 医学部, 助手 (40210009)
MIZUNO Akira  The University of Tokushima Medical School Hospital, Instructor, 医学部附属病院, 助手 (80219641)
NOMA Yoshihiko  The University of Tokushima Medical School Hospital, Lecturer, 医学部附属病院, 講師 (10218349)
KUWAJIMA Masamichi  The University of Tokushima School of Medicine, Associate Professor, 医学部, 助教授 (00205262)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsTvpe2DM / beta-cell proliferation / beta-cell mass / insulin secretion / insulin resistance / microangiopathy / fat droplet / OLETF / LETO / 部分膵切除 / β細胞増殖能 / 胎児ラ氏島様細胞集塊 / β細胞量 / 膵管上皮細胞 / β細胞インスリン含量
Research Abstract

In this study, we tried to explore whether an impairment of insulin secretion observed in type 2 diabetes mellitus is caused by the reduction of beta -cell mass using OLETF rats, a model of type 2 diabetes. The following results have been obtained ;
1. A failure in the compensative proliferation of pancreatic beta-cells has been reported in the OLETF rat. The present study was undertaken to define whether the defect is involved in its fetal model. The defective morphogenesis of endocrine cells and functional adaptation to increased metabolic demand could be thought of as a failure involved in the fetal model, and a decreased expression of PDX- 1 may be one of the factors which contribute to this failure in this model rat.
2. Hypertriglyceridemia resulted in significant TG stores in the islets, which subsequently inhibited glucose-induced insulin secretion, at least in part, via reduced glucokinase activity in the islets Fat droplets in the islets may play an important role in hastening the development of diabetes mellitus in this rat model.
3. The fine capillaries that form a network in the islets were extremely sparse in the OLETF rat, resulting in a defective glomerular-like configuration, whereas those from the control rat (LETO) were dense, forming a nearlv typical glomerular-like configuration.
4. Wistar fatty rat, another type 2 model, has a poor capacity for proliferation of pancreatic beta -cells, which causes the onset of overt diabetes along with insulin resistance due to extreme obesity just like OLETF rats.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] K.Shima: "Exercise training in Otsuka Long-Evans Tokushima Fatty rat,a model of spontaneous non-insulin dependent diabetes mellitus:effects on the B-cell mass,insulin content and fibcosis in the pancreas." Diab.Res.Clin.Pract.35. 11-19 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.Mizuno: "Extrapancreatic action of truncated glucagon-like peptide-1 Otsuka Long-Evans Tokushima Fatty rats,an animal model for non-insulin.dependent diabetes mellitus." Metabolism. 46. 745-749 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Z.W.Man: "Impaired β-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in CLETF rat,a model of spontaneous NIDDM." Diabetes. 46. 1718-1724 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Toide: "Glucose transporter levels in a male spontaneous non-insulin-dependent diabetes mellitus-rat of the Otsuka Long-Evans Tokushima Fatty strain." Diab.Res.Clin.Pract.38. 151-161 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Sakamoto: "Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat,a model of spontaneous NIDDM" Diabetes. 47. 82-86 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Zhu: "Ovarian hormone-induced beta-cell hypertrophy contributes to the homeostatic control of beta-cell mass in OLETF female rat,a model of type2 diabetes." Diabetologia. 41. 799-805 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Shima, M.Zhu, Y.Noma, A.Mizuno, T.Murakami, T.Sano and M.Kuwajima: "Exercise training in Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin dependent diabetes mellitus : effects on the B-cell mass, insulin content and fibrosis in the pancreas" Diab. Res. Clin. Pract. 35 (1). 11-19 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.Mizuno, M.Kuwajima, K.Ishida, Y.Noma, T.Murakami, K.Tateishi, I.SatoandK.Shima: "Extrapancreatic action of truncated glucagon-like peptide-1 in Otsuka Long-Evans Tokushima Fatty rats, an animal model for non-insulin-dependent diabetes mellitus." Metabolism. 46 (7). 745-749 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Z.W.Man, M.Zhu, Y.Noma, K.Toide, T.Sato, Y.Asahi, T.Hirashima, S.Mori, K.Kawano, A.Mizuno, T.Sano and K.Shima: "Impaired beta-cell function and deposition of fat droplets in the pancrease as a consequence of hypertriglyceridemia in OLETF rat, a model of spontaneous NIDDM." Diabetes. 46. 1718-1724 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Toide, Z.W.Man, Y.Asahi, T.Sato, N.Nakayama, Y.Noma, Y.Oka, K.Shima: "Glucose transporter levels in a male spontaneous non-insulin-dependent deabetes mellitus rat of the Otsuka Long-Evans Tokushima Fatty strain." Diab.Res.Cin.Pract. 38. 151-161 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Sakamoto, K.Minami, Y.Niwa, M.Ohnaka, Y.Nakaya, A.Mizuno, M.Kuwajima and K.Shima: "Effect of exercise traning and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM." Diabetes. 47. 82-86 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Zhu, A.Mizuno, M.Kuwajima, T.Ogino, T.Murakami, Y.Noma, T.Sano and K.Shima: "Ovarian hormone-induced beta-cell hypertrophy contributes to the homeostatic control of beta-cell mass in OLETF female rat, a model of type 2 diabetes" Diabetologia. 41. 799-805 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.shima: "Exercise training in ocsuka Long-Evans Tokushima Fatty rat,a model of spantaneous noninsulin dependent diabetes mellicus:effects on the B-cell mass,insulin content and fibrasis in the panareas." Diab.Res.Clin.Pract.35(1). 11-19 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.Mizuno: "Extrapancreatic action of truncated glucagon-like peptid-1 in Ocsuka Long-EvansYokushimaFatty rats,an animal model for non-dependent diabeces mellitus." Metabolism. 46(7). 745-749 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Z.W.Man: "Impaired β-cell function and deposition of fat droplets in the pancrease as a consequence of hypertriglyceridemin in OLETF rat,a model of sportaneous NIDDM." Diabetes. 46. 1718-1724 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Toide: "Glucase transporter levels in a mole spontaneous non-insulin-depe dent diaberes mellitus rat of the Otsuka Long-Evans Tokushima Fatty strain." Dinb.Res.Clin.Pract.38. 151-161 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Sakamoto: "Effect of exereise training and food restriction on enclotheliwn-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat,a model of spontaneous NIDDM" Diabetes. 47. 709-805 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Zhu: "Ovarian hormone-induced beta-cell hypertrophycontributes to the homeostatic control of beta-cell mass in OLETF female rat,amodel of type 2 diabetes." Diabetologia. 41. 709-805 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kenji Shima: "exercise in Otsuka Long-Evans Tokushima Fatty rat,a model of spontareous non-insulin-dependent diabetes mellitus;effects on the B-cell mass,insulin content and fibrosis in the pancreas." Diabetes Research Clinical Practice. 35. 11-19 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Akira Mizuno: "Extrapancreatic action of truncated glucagon-like peptide-I in Otsuka Long-Evans Tokushima Fatty rat,an annimal model for Non-Insulin-Dependent Diabetes Mellitus." Metabolism. 46(7). 745-749 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Zhi-Wei Man: "Impaired B-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in OLETF rat a model of spontaneous NIDDM" Diabetes. 46. 1718-1723 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kiyotaka Toide: "Glucose transporter levels in a male spontaneous non-insulin-dependent diabetes mellitus rat of the Otsuka Long-Evans Tokushima Fatty strain." Diabetes Research Clinical Practice. 38. 151-161 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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