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Analysis of pathogenic factors of type 2 diabetes mellitus by stable-labeled minimal model approach

Research Project

Project/Area Number 12671123
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAGASAKA Shoichiro  Jichi Medical School, Department of Medicine, Lecturer, 医学部, 講師 (00296112)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA San-e  Jichi Medical School, Department of Medicine, Assistant Professor, 医学部, 教授 (70112620)
KUSAKA Ikuyo  Jichi Medical School, Department of Medicine, Assistant, 医学部, 助手 (30285788)
NAKAMURA Tomoatsu  Jichi Medical School, Department of Medicine, Assistant, 医学部, 助手 (10296113)
斉藤 寿一  自治医科大学, 医学部, 教授 (10048994)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsminimal model / stable-glucose / glucose metabolism / insulin sensitivity / IGT / Endogenous glucose production / Diabetes mellitus
Research Abstract

Glucose mass action may be overestimated and insulin sensitivity underestimated in the single compartment minimal model analysis of frequently sampled intravenous glucose tolerance test (FSIGT). Additional use of stable-labeled glucose allows us to precisely estimate indexes for glucose uptake stimulated by insulin (Si^<2*>) and by glucose (Sg^<2*>), and to illustrate time course changes in endogenous glucose production (EGP) in the two compartment model (Diabetes 48 : 1054-1060, 1999). To clarify pathogenic factors responsible for glucose intolerance using this stable-labeled insulin-modified FSIGT, 20 non-obese subjects with type 2 diabetes mellitus (BMI 20.6±0.6kg/m^2 and HbA_1c8.0±0.4%), 8 with impaired glucose tolerance (IGT), and 20 with normal glucose tolerance (NGT) were evaluated. Kg values were 1.93±0.11%/min in NGT, 1.38±0.18 in IGT, and 1.06±0.08 in diabetes (P<0.0001). Acute insulin response to the glucose bolus (AIR) was also deteriorated in this order (P<0.0001). There w … More ere no differences in Si^<2*> and Sg^<2*> among these three groups. Basal EGP was 1.53±0.06mg/kg.min in NGT, 1.69±0.16 in IGT and 1.84±0.08 in diabetes (P=0.0246). There was a linear relationship between basal EGP and fasting plasma glucose (r=0.486, P=0.0005). The initial suppression (0-20min) of EGP was virtually identical between NGT and IGT, but was blunted in diabetes. Thus, in IGT subjects, the decreased net glucose uptake in peripheral tissue, due to the decline in AIR, would be important for the glucose intolerance, since the regulation of EGP was not so impaired. In diabetic subjects, along with the further decline in AIR, the EGP regulation was severely deteriorated. In conclusion, there was no decrease in insulin action and glucose mass action to stimulate glucose uptake in the non-obese glucose intolerant subjects of this study. Together with the progression from IGT to full blown diabetes, the EGP dysregulation came to be evident in concordance with the further decline in AIR. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] 徳山 薫平, 長坂 昌一郎, 草鹿 育代, 中村 友厚, 石川 三衛: "内因性糖放出についてのインスリン感受性の2-comparlment modelによる解析"糖尿病. 44. 813-818 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kumpei Tokuyama, Shoichiro Nagasaka, Ikuyo Kusaka, Tomoatsu Nakamura, San-e Ishikawa, Toshikazu Saito, Masami Toyama, Yuichiro Nishida, Akira Kiyonaga, Hiroaki Tanaka: "Insulin sensitivity suppressing endogenous glucose production assessed by a 2-compartment model"J. Japan Diab. Soc.. 44. 813-818 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 徳山薫平, 長坂昌一郎, 草鹿育代, 中村友厚, 石川三衛, 他: "内因性糖放出についてのインスリン感受性の2-compartment modelによる解析"糖尿病. 44. 813-818 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura T, Nagasaka S, Ishikawa S, Kusaka I, et al.: "Clinical implication of serial leptin measurement in subjects with type 2 diabetes mellitus"Endocrine J. 48. 87-94 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniguchi A, Nagasaka S, et al.: "Serum nonesterified fatty acid are related with carotid atherosclerotic plaque in nonobese nonhypertensive Japanese type 2 diabetic patients"Diabetes Care. 24. 1505-1507 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukushima M, Nagasaka S, et al.: "Remnant-like particle cholesterol and insulin resistance in nonobese nonhypertensive Japanese glucose-tolerant relatives of type 2 diabetic patients"Diabetes Care. 24. 1691-1694 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniguchi A, Nagasaka S, et al.: "Serum nonesterified fatty acids are increased in nonobese Japanese type 2 diabetic patients with microalbuminuria"Diabetes Care. 24. 1847-1849 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Taniguchi A, Nagasaka S, et al.: "Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients"Metabolism. 50. 477-480 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 長坂昌一郎, 宮本佳代子, 松田康子: "健康21シリーズ(1)糖尿病の人の食事"女子栄養大学出版部. 151 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura T,Nagasaka S, et al: "Crucial role of insulin in leptin maintenance : profound decrease in serum leptin by octreotide acetate in insulinoma subjects"Endocrine J. 47(3). 359-364 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Taniguchi A,Nagasaka S, et al: "The role of the body mass index and triglyceride levels in identifying insulin-sensitive and insulin-resistant varinats in Japanese non-insulin-dependent diabetic patients"Metabolism. 49(8). 1001-1005 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamura T,Nagasaka S, et al: "Association of hyperthyroidism with serum leptin levels"Metabolism. 49(10). 1285-1288 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Taniguchi A,Nagasaka S, et al: "Remnant-like particle cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients"Diabetes Care. 23(12). 1766-1769 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamura T,Nagasaka S, et al: "Crucial role of insulin in leptin maintenance : profound decrease in serum leptin by octreotide acetate in insulinoma subjects"Endocrine J. 47(3). 359-364 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Taniguchi A,Nagasaka S, et al: "The role of the body mass index and triglyceride levels in identifying insulin-sensitive and insulin-resistant varinats in Japanese non-insulin-dependent diabetic patients"Metabolism. 49(8). 1001-1005 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamura T,Nagasaka S, et al: "Association of hyperthyroidism with serum leptin levels"Metabolism. 49(10). 1285-1288 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Taniguchi A,Nagasaka S, et al: "Remnant-like particle cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients"Diabetes Care. 23(12). 1766-1769 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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