Intramyocellular lipid and insulin resistance: A longitudinal in vivo (1)H-spectroscopic study in Zucker diabetic fatty rats

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 (1)H-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.