The Effects of Rosiglitazone on Insulin Sensitivity, Lipolysis, and Hepatic and Skeletal Muscle Triglyceride Content in Patients With Type 2 Diabetes
Abstract
We examined the effect of three months of rosiglitazone treatment (4 mg b.i.d.) on whole-body insulin sensitivity and in vivo peripheral adipocyte insulin sensitivity as assessed by glycerol release in microdialysis from subcutaneous fat during a two-step (20 and 120 mU · m−2 · min−1) hyperinsulinemic-euglycemic clamp in nine type 2 diabetic subjects. In addition, the effects of rosiglitazone on liver and muscle triglyceride content were assessed by 1H-nuclear magnetic resonance spectroscopy. Rosiglitazone treatment resulted in a 68% (P < 0.002) and a 20% (P < 0.016) improvement in insulin-stimulated glucose metabolism during the low- and high- dosage−insulin clamps, respectively, which was associated with ∼40% reductions in plasma fatty acid concentration (P < 0.05) and hepatic triglyceride content (P < 0.05). These changes were associated with a 39% increase in extramyocellular lipid content (P < 0.05) and a 52% increase in the sensitivity of peripheral adipocytes to the inhibitory effects of insulin on lipolysis (P = 0.04). In conclusion, these results support the hypothesis that thiazolidinediones enhance insulin sensitivity in patients with type 2 diabetes by promoting increased insulin sensitivity in peripheral adipocytes, which results in lower plasma fatty acid concentrations and a redistribution of intracellular lipid from insulin responsive organs into peripheral adipocytes.
Footnotes
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Address correspondence and reprint requests to Kitt F. Petersen, M.D., Department of Internal Medicine, Yale University School of Medicine, 333 Cedar St., Fitkin 1, Box 208020, New Haven, CT 06520-8020. E-mail: kitt.petersen{at}yale.edu.
Received for publication 3 October 2001 and accepted in revised form 31 October 2001.
S.E.I. has received honoraria and is on the speakers’ bureau for both Glaxco/SmithKline and Takeda Pharmaceuticals America and has also received research support from Takeda. G.I.S. has served as a research consultant for Glaxo/SmithKline Beecham.
DEXA, dual-energy X-ray absorptiometry; EMLC, extramyocellular lipid content; GDR, glucose disposal rate; ETOH, ethanol; ETOHin, ethanol concentration measured in the perfusate; ETOHout, ethanol concentration in the dialysate; GCMS, gas chromatography−mass spectrometry; GIR, glucose infusion rate; GP, endogenous glucose production; IMLC, intramyocellular lipid content; NMR, nuclear magnetic resonance; PPAR-γ, peroxisome proliferator−activated receptor-γ; TNF-α, tumor necrosis factor-α; TZD, thiazolidinedione.
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