Intramyocellular lipid and insulin resistance: a longitudinal in vivo 1H-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.
Kuhlmann
Johanna
J
Aventis Pharma Deutschland, Frankfurt am Main, Germany.
Neumann-Haefelin
Claudia
C
Belz
Ulrich
U
Kalisch
Jürgen
J
Juretschke
Hans-Paul
HP
Stein
Marion
M
Kleinschmidt
Elke
E
Kramer
Werner
W
Herling
Andreas W
AW
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D008099:Liver / Q000473:pathology; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists
D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone