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Pathophysiology

Circulating Concentrations of the Adipocyte Protein Adiponectin Are Decreased in Parallel With Reduced Insulin Sensitivity During the Progression to Type 2 Diabetes in Rhesus Monkeys

  1. Kikuko Hotta1,
  2. Tohru Funahashi1,
  3. Noni L. Bodkin2,
  4. Heidi K. Ortmeyer2,
  5. Yukio Arita1,
  6. Barbara C. Hansen2 and
  7. Yuji Matsuzawa1
  1. 1Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
  2. 2Obesity and Diabetes Research Center, Department of Physiology, University of Maryland, Baltimore, Maryland
    Diabetes 2001 May; 50(5): 1126-1133. https://doi.org/10.2337/diabetes.50.5.1126
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      FIG. 1.

      Fat weight (A) and the plasma levels of leptin (B) and adiponectin (C) in lean, hyperinsulinemic obese, and type 2 diabetic rhesus monkeys. The plasma levels of adiponectin and leptin from lean (n = 14), obese (n = 23), and type 2 diabetic (n = 10) monkeys were measured by ELISA. Values represent means ± SE. * P < 0.05; ** P < 0.01; *** P < 0.001.

    • FIG. 2.
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      FIG. 2.

      Longitudinal changes in plasma adiponectin, plasma leptin, body weight, fat weight, plasma glucose, plasma insulin, M rate, and KG. The plasma levels of adiponectin and leptin were analyzed by ELISA. M rate was determined by a hyperinsulinemic-euglycemic clamp, as described in research design and methods. Data are shown as means ± SE. n = 7 in phase 1, n = 14 in phase 2, n = 14 in phase 3, n = 11 in phase 4, n = 7 in phase 5, n = 6 in phase 6, n = 16 in phase 7, and n = 12 in phase 8.

    • FIG. 3.
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      FIG. 3.

      Correlation between M rate and plasma adiponectin in 24 independent nondiabetic monkeys. M rate was determined by the hyperinsulinemic-euglycemic clamp method, as described in research design and methods. The plasma levels of adiponectin were analyzed by ELISA. r = 0.66; P < 0.001.

    • FIG. 4.
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      FIG. 4.

      Plasma adiponectin (A), body weight (B), fat weight (C), M rate (D), fasting plasma insulin (E), and fasting plasma glucose (F) in lean (□), obese with hyperadiponectinemia ([cjs2113]), and obese with hypoadiponectinemia (▪) monkeys. The plasma levels of adiponectin were analyzed by ELISA. ** P < 0.01; *** P < 0.001.

    • FIG. 5.
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      FIG. 5.

      Amino acid sequence and expression of rhesus monkey adiponectin. A: Comparison of the amino acid sequences from monkey and human adiponectin. Amino acids that are identical to the monkey sequence are represented by dashed lines. The predicted signal sequence is underlined. The glycine in a region encoding Gly-X-Y triplets (Glys-X-Y repeats) is indicated in bold type. The noncollagenous region, which is homologous to VIII collagen, X collagen, and the C chain of C1q, is double-underlined. B: Tissue distribution of monkey adiponectin mRNA. Total RNA (10 μg) isolated from various tissues was applied to each lane. Northern blot analysis was carried out as described in research design and methods.

    • FIG. 6.
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      FIG. 6.

      A: The correlation between mRNA levels of adiponectin and fat weight (r = –0.11, NS) and between mRNA levels of ob (leptin) and fat weight (r = 0.62, P = 0.01). A total of 5 μg of total RNA was electrophoresed. Hybridization was performed as described in research design and methods. B: Correlation between the plasma and mRNA levels of adiponectin (r = –0.02, NS) and between the plasma leptin and ob mRNA levels of (r = 0.60, P = 0.01). The mRNA levels of adiponectin and ob were determined by Northern blot hybridization. The plasma levels of adiponectin and leptin were analyzed by ELISA.

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    Circulating Concentrations of the Adipocyte Protein Adiponectin Are Decreased in Parallel With Reduced Insulin Sensitivity During the Progression to Type 2 Diabetes in Rhesus Monkeys
    Kikuko Hotta, Tohru Funahashi, Noni L. Bodkin, Heidi K. Ortmeyer, Yukio Arita, Barbara C. Hansen, Yuji Matsuzawa
    Diabetes May 2001, 50 (5) 1126-1133; DOI: 10.2337/diabetes.50.5.1126

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    Circulating Concentrations of the Adipocyte Protein Adiponectin Are Decreased in Parallel With Reduced Insulin Sensitivity During the Progression to Type 2 Diabetes in Rhesus Monkeys
    Kikuko Hotta, Tohru Funahashi, Noni L. Bodkin, Heidi K. Ortmeyer, Yukio Arita, Barbara C. Hansen, Yuji Matsuzawa
    Diabetes May 2001, 50 (5) 1126-1133; DOI: 10.2337/diabetes.50.5.1126
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