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Research of Novel Mechanism in the Genesis of Diabetes Mellitus: The Dysfunction of pancreatic beta cell by the Increase of Blood Lipid Peroxides

Research Project

Project/Area Number 13671202
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionNippon Medical School

Principal Investigator

OIKAWA Shinichi  Nippon Medical School, Professor, 医学部, 教授 (30142946)

Co-Investigator(Kenkyū-buntansha) MIYAZAWA Teruo  Tohoku University Graduate School of Life Science and Agriculture, Professor, 大学院・農学研究科, 教授 (20157639)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordspancreatic β-cell / oxidized stress / insulin secretion / lipid peroxide / Hit-Y15 cell / oxLDL / 糖尿病 / 酸化LDL / β細胞
Research Abstract

It is believed that lipid peroxidation is a main mechanism in atherogenesis from the various studies on the relationships between lipid peroxides and vascular cells. However, its effect on the other cell types has not been studied. It has been suggested that insulin secretary cell of pancreas (β-cell) was weak for oxidized stress. Therefore we challenged Hit-T15 cell, which is a β-cell derived from hamster pancreatic tumor cell, to clarify the effect of phospholipid peroxides on insulin secretion. We added native phosphatidylcholine (PC), phosphatidylcholine hydroperoxide (PCOOH) and lysophosphatidylcholine (LysoPC) in the culture of HIT-T15 cell. LysoPC significantly decreased the expression of preproinsulin mRNA, intracellular insulin content, and insulin secretion. PCOOH effect did not affect on the preproinsulin mRNA expression, but decreased intracellular insulin level and insulin secretion. These oxidized phospholipids would be the components of oxidized LDL (oxLDL). Therefore we studied the effect of oxLDL in the similar experiments as Hit-T15cell culture with LysoPC as comparison with native LDL (nLDL) and acerylated LDL (AcLDL). OxLDL significantly decreased the expression of preproinsulin mRNA, intracellular insulin content, and insulin secretion as same as LysoPC. On the other hand nLDL or AcLDL had no effects. LysoPC and oxLDL did not affect MTT assay as evaluation of cell viability. These results suggested that oxLDL disturbed insulin metabolism of β-cell to decrease insulin secretion via PCOOH and PC. We proposed that oxidized stress would be diabetogenic by the effect of oxLDL.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Shuto Y, Oikawa S, et al.: "Hypothalamic growth hormone secretagogue receptor regulated growth hormone secretion, feeding and adipposity"J Clin Invest. 109. 1429-1436 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kotake H, Oikawa S, et al.: "Effect of HMG-CoA reductase inhibitor on plasma cholesteryl ester transfer protein activity in primary hypercholesterolemia : Comparison among CETP/Taq1B"J Atheroscler Thromb. 9. 207-212 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mabuchi H, Oikawa S, et al.: "Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia-secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT)"Circ J. 66. 1096-1100 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuzaki M, Oikawa S, et al.: "Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia-Primary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT)"Circ J. 66. 1087-1095 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishii S, Oikawa S, et al.: "Role of Ghrelin in Streptozotocin-Induced Diabetic Hyperphagia"Endocrinology. 143. 4934-4937 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura H, Oikawa S, et al.: "Ghrelin stimulates GH but not food intake in arcuate nucleus ablated rats"Endocrinology. 143. 3268-3275 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shuto Y, Shibasaki T, Wada K, Parhar I, Kamegai J, Sugihara H, Oikawa S, Wakabayashi I: "Generation of polydonal antiserum against the growth hormone secretagogue receptor (GHS-R) evidence that the GHS-R exists in the hypothalamus, pituitary and stomach of rats."Life Science. 68(9). 991-996 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toyota T, Oikawa S, Abe R, Sano R, Suzuki N, Hisamichi S, Fukao A: "Cilostazol Diabetes Mellitus Lipids Study Group: Effect of cilostazol on lipid, uric acid and glucose metabolism in patients with impaired glucose tolerance or type 2 diabetes mellitus. A double -blind, placebo-controlled study."Clin Drug Invest. 21(5). 325-335 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Oikawa S: "Regulation of the ghrelin gene: Growth hormone-releasing hormone upregulates ghrelin mRNA in the pituitary."Endocrinology. 142(9). 4154-4157 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naito T, Oikawa S, Kotake H, Hayasaka K, Toyota T: "Effect of glucose concentration on foam cell formation in THP-1 cell."J Atheroscler Thoromb. 8(2). 55-62 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Ishigaki Y, Oikawa S, Yamamoto T: "Role of apolipoprotein E variants in lipoprotein glomerulopathy and other renal diseases."Clin Exp Nephrol. 5(4). 201-208 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toyota T, Oikawa S: "the Beraprost Sodium Study Group: Effects of beraprost Sodium (Domer) in patients with diabetes mellitus complicated by chronic arterial obstruction."Angiology. 53(1). 7-13 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Ishigaki Y, Oikawa S, Yamamoto T: "Etiological significance of apolipoprotein E mutations in lipoprotein glomerulopathy."Trends Cardiovasc Med. 12(2). 63-67 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagashima T, Oikawa S, Hirayama Y, Tokita Y, SeMkawa A, Ishigaki Y, Yamada R, Miyazawa T: "Increase of serum phosphatidylcholine hydroperoxide dependent on glycemic control in type 2 diabetic patients."Diab Res din Pract. 56(1). 19-25 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka S, Tanabe Y, Tamura H, Ishii S, Shuto Y, Kamegai J, Sugihara H, Kobayashi M, Wakabayashi I, Murano T, Shirai K, Oikawa S: "Chylomicronemia caused by lipoprotein lipase gene mutation related to a hyper-response of insulin secretion to glucose."Int Med.. 41(4). 300-303 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shuto Y, Shibasaki T, Otagiri A, Kuriyama H, Ohata H, Tamura H, Kamegai J, Sugihara H, Oikawa S, Wakabayashi I: "Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion feeding, and adipposity."J Clin Invest. 109(11). 1429-1436 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura H, Kamegai J, Shimizu T, Ishii S, Sugihara H, Oikawa S: "Ghrelin stimulates GH but not food intake in arcuate nucleus ablated rats."Endocrinology. 143(9). 3268-3275 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishii S, Kamegai J, Tamura H, Shimizu T, Sugihara H, Oikawa S: "Role of ghrelin in streptozotocin-induced diabetic hyperphagia."Endocrinology. 143(12). 4934-4937 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuzaki M, Kita T, Mabuchi H, Matsuzawa Y, Nakaya N, Oikawa S, Saito Y, Sasaki J, Shimamoto K, Itakura H, and the J-LIT Study group: "Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholersterolemia-Primary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT)-"Circ J. 66(12). 1087-1095 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mabuchi H, Kita T, Mabuchi H, Matsuzaki M, Matsuzawa Y, Nakaya N, Oikawa S, Saito Y, Sasaki J, Shimamoto K, Itakura H, and the J-LIT Study group: "Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholersterolemia-Secondary prevention cohort study of the Japan Upid Intervention Trial (J-LTT)-"Circ J. 66(12). 1096-1100 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kotake H, Sekikawa A, Tokita Y, Ishigaki Y, Oikawa S: "Effect of HMG-CoA reductase inhibitor on plasma cholesteryl ester transfer protein activity in primary hypercholesterolemia: Comparison among CETP/Taq1B genotype subgroups."J Atheroscler Thromb. 9(5). 207-212 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shuto Y, Oikawa S, et al.: "Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adipposity"J Clin Invest. 109・11. 1429-1436 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kotake H, Oikawa S, et al.: "Effect of HMG-CoA reductase inhibitor on plasma cholesteryl ester transfer protein activity in primary hypercholesterolemia : Comparison among CETP/Taq1B"J Atheroscler Thromb. 9・5. 207-212 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mabuchi H, Oikawa S, et al.: "Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholersterolemia-Secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT)"Circ J. 66・12. 1096-1100 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuzaki M, Oikawa S, et al.: "Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholersterolemia-Primary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT)"Circ J. 66・12. 1087-1095 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishii S, Oikawa S, et al.: "Role of ghrelin in streptozotocin-induced diabetic hyperphagia"Endocrinology. 143・12. 4934-4937 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamura H, Oikawa S, et al.: "Ghrelin stimulates GH but not food intake in arcuate nucleus ablated rats"Endocrinology. 143・9. 3268-3275 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagashima T, Oikawa S, et al.: "Increase of serum phosphatidylcholine hydroperoxide dependent on glycemic conttrol in type 2 diabetic patients"Diabetes Res Clin Pract. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Saito T, Ishigaki Y, Oikawa S, Yamamoto T: "Etiological significance of lipoprotein E mutations in lipoprotein glomerulopathy"Trends Cardiovasc Med. 12(2). 63-67 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kamegai J, Tamura H, Oikawa S, et al.: "Regulation of the ghrelin gene : Growth hormone-releasing hormone upregulates ghrelin mRNA in the pituitary"Endocrinology. 142(9). 4154-4157 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Naito T, Oikawa S, et al.: "Effects of glucose concentration on foam cell formatiion in THP-1 cells"J Atheroscler Thromb. 8(2). 55-62 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Toyota T, Oikawa S, et al.: "Effect of cilostazol on lipid, uric acid and glucose metabolism inpatients With impaired glucose"Clinical Pharmacodynamics. 21(5). 325-335 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shuto Y, Shibasaki T, Oikawa S, et al.: "Generation of polyclonal antiserum against the growth hormone secretagogue receptor (GHS-R) evidence that the GHS-R exists in the hypothalamus, pituitary and stomach of rats"Life Science. 68. 991-996 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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