Johanna Kuhlmann

Correlation between insulin resistance and intramyocellular lipid levels in rats

Increased intramyocellular lipid (IMCL) content has been proposed as biomarker for insulin resistance (IR). An inverse correlation between IMCL and insulin sensitivity (IS) was found in nonathletic humans, whereas in animal models only a few validation studies have been performed. The aim of this study was to investigate the interrelation between IS indices determined by the glucose clamp technique (glucose disposal (GD), exogenous glucose infusion rates (GIR)) and IMCL content in the tibialis (TIB) and the soleus (SOL) muscle obtained by magnetic resonance spectroscopy in different rat models of IR. Diet‐induced insulin‐resistant Wistar rats as well as genetic disease models (ZDF rats) were used. In both muscles, elevated IMCL correlated with an impaired IS in all models of IR. The correlation of IMCL with both parameters for IS was comparable in TIB and SOL. The best fit between IMCL and IS was obtained using TIB and GIR data (r = −0.69, P < 0.001). Diabetic male ZDF rats exhibited comparatively low IMCL levels due to their catabolic state: exclusion of this group improved r. In summary, IMCL, especially in TIB, is a valid biomarker for IS in various rat models of IR with the advantage of a fast repeatable noninvasive measurement in individual animals. Magn Reson Med 53:1275–1282, 2005.

Determinants of intramyocellular lipid concentrations in rat hindleg muscle.

The investigation of intramyocellular lipids (IMCLs) with proton MR spectroscopy (1H‐MRS) in humans has recently received increasing attention. IMCL levels correlate with insulin resistance and are affected by diet and exercise, making IMCL an interesting marker for metabolic investigations. In the present in vivo study, the feasibility of using 1H MRS for the detection of IMCL in rats is demonstrated, and the influence of various factors, such as age, gender, muscle type, and rat strain, on IMCL levels is systematically analyzed. In healthy Wistar and Sprague Dawley (SD) rats, the highest ratios of IMCL/tCr were found in young rats, and IMCL/tCr decreased with increasing age. In addition, IMCL concentration was clearly influenced by gender and muscle type. Insulin‐resistant, male, obese, Zucker diabetic fatty (ZDF) rats showed significantly higher IMCL levels than Wistar or SD rats. In conclusion, although IMCL levels are clearly influenced by insulin resistance, several other factors influence IMCL levels, such as age, gender, muscle type, and rat strain. Therefore, when using IMCL as a surrogate marker for insulin resistance, it is necessary to carefully compare results with age‐ and gender‐matched controls, and to use identical conditions. Magn Reson Med 50:242–248, 2003.