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Diabetes 52:138-144, 2003
© 2003 by the American Diabetes Association, Inc.

Intramyocellular Lipid and Insulin Resistance

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

Johanna Kuhlmann, Claudia Neumann-Haefelin, Ulrich Belz, Jürgen Kalisch, Hans-Paul Juretschke, Marion Stein, Elke Kleinschmidt, Werner Kramer, and Andreas W. Herling

From Aventis Pharma Deutschland, Frankfurt am Main, Germany

Insulin resistance plays an important role in the pathogenesis of human type 2 diabetes. In humans, a negative correlation between insulin sensitivity and intramyocellular lipid (IMCL) content has been shown; thus, IMCL becomes a marker for insulin resistance. Recently, magnetic resonance spectroscopy (MRS) has been established as a dependable method for selective detection and quantification of IMCL in humans. To validate the interrelation between insulin sensitivity and IMCL in an animal model of type 2 diabetes, we established volume selective 1H-MRS at 7 Tesla to noninvasively assess IMCL in the rat. In male obese Zucker Diabetic Fatty rats and their lean littermates, IMCL levels were determined repeatedly over 4 months, and insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp method at 6–7 and at 22–24 weeks of age. A distinct relation between IMCL and insulin sensitivity was demonstrated as well as age dependence for both parameters. Rosiglitazone treatment caused a clear reduction of IMCL and hepatic fat despite increased body weight, and a marked improvement of insulin sensitivity. Thus, the insulin sensitizing properties of rosiglitazone were consistent with a redistribution of lipids from nonadipocytic (skeletal muscle, liver) back into fat tissue.


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