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Pathophysiology

Intramyocellular Lipid and Insulin Resistance

A Longitudinal In Vivo 1H-Spectroscopic Study in Zucker Diabetic Fatty Rats

  1. Johanna Kuhlmann,
  2. Claudia Neumann-Haefelin,
  3. Ulrich Belz,
  4. Jürgen Kalisch,
  5. Hans-Paul Juretschke,
  6. Marion Stein,
  7. Elke Kleinschmidt,
  8. Werner Kramer and
  9. Andreas W. Herling
  1. From Aventis Pharma Deutschland, Frankfurt am Main, Germany
    Diabetes 2003 Jan; 52(1): 138-144. https://doi.org/10.2337/diabetes.52.1.138
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    • FIG. 1.
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      FIG. 1.

      A: Representative volume of selective in vivo 1H-MR spectra at 7 Tesla of the M. tibialis anterior of an obese ZDF rat (20 weeks old, ∼470 g) derived from different volume sizes: 4 mm3, 1,024 averages (a); 8 mm3, 512 averages (b); and 18 mm3, 256 averages (c). Reduction of the selected volume diminishes the EMCL signal at 1.5 ppm and facilitates the quantification of IMCL at 1.3 ppm. Spectra were referenced to the tCr resonance at 3.05 ppm. B: Representative volume of selective in vivo 1H-MR spectra at 7 Tesla of the M. tibialis anterior of a lean ZDF rat (a) and an obese ZDF rat (b). Both rats were ∼8 weeks old. Volume: 8 mm3. Note the elevated IMCL-to-tCr integral ratio in the spectrum of the obese ZDF rat as compared with the lean littermate.

    • FIG. 2.
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      FIG. 2.

      In vivo 1H-MRS data for IMCL/tCr in M. soleus (A) and M. tibialis anterior (B) in lean (white bars) and obese (black bars) ZDF rats (protocol A). Values are means ± SE, n = 7–8. For the respective age, all values were significantly different (P < 0.001) between lean and obese rats. *P < 0.001 vs. value at 6 weeks of age for the respective rat group.

    • FIG. 3.
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      FIG. 3.

      Body weight (A), blood glucose (B), cholesterol (C), insulin (D), FFA (E), and triglyceride (F) in lean control (white circles), obese control (black circles), and obese RGZ-treated (black squares) ZDF rats (protocol C). Plasma parameters were obtained during nonstarved conditions. Values are means ± SE, n = 7–8.

    • FIG. 4.
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      FIG. 4.

      Representative in vivo 1H-MR spectra of liver in lean control (a), RGZ-treated obese (b), and obese control ZDF rat (c) at the age of 17 weeks (protocol C). Spectra show water signal at 4.7 ppm and fat resonance at 1.3 ppm.

    • FIG. 5.
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      FIG. 5.

      In vivo 1H-MRS data for IMCL/tCr in M. tibialis anterior in lean control (white bars), obese control (black bars), and obese RGZ-treated (grey bars) ZDF rats at the ages of 16 and 22 weeks (protocol C). Values are means ± SE, n = 6–8. *P < 0.001.

    Tables

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    • TABLE 1

      Mean values of GIR (mg · kg−1 · min−1) and FFA (mmol/l) during euglycemic-hyperinsulinemic glucose clamp studies in lean and obese ZDF rats

      Age (weeks)ZDF rat groupsGIRFFA (mmol/l)
      BasalClamp
      6–7Lean20.2 ± 0.80.58 ± 0.060.06 ± 0.01
      6–7Obese2.7 ± 0.8*1.07 ± 0.02*0.52 ± 0.04*
      22–24Lean14.4 ± 0.50.45 ± 0.030.04 ± 0.01
      22–24Obese1.6 ± 0.6*0.64 ± 0.05†0.15 ± 0.03†
      22–24Obese+RGZ6.7 ± 0.8+1.05 ± 0.06‡0.26 ± 0.04§
      • Data are means ± SE; n = 5–8;

      • *

        * P < 0.001,

      • †

        † P < 0.05 vs. age-matched lean control;

      • ‡

        ‡ P < 0.001,

      • §

        § P < 0.05 vs. age-matched obese control.

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    Intramyocellular Lipid and Insulin Resistance
    Johanna Kuhlmann, Claudia Neumann-Haefelin, Ulrich Belz, Jürgen Kalisch, Hans-Paul Juretschke, Marion Stein, Elke Kleinschmidt, Werner Kramer, Andreas W. Herling
    Diabetes Jan 2003, 52 (1) 138-144; DOI: 10.2337/diabetes.52.1.138

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    Intramyocellular Lipid and Insulin Resistance
    Johanna Kuhlmann, Claudia Neumann-Haefelin, Ulrich Belz, Jürgen Kalisch, Hans-Paul Juretschke, Marion Stein, Elke Kleinschmidt, Werner Kramer, Andreas W. Herling
    Diabetes Jan 2003, 52 (1) 138-144; DOI: 10.2337/diabetes.52.1.138
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