The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes.
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 (1)H-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 approximately 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.
Mayerson
Adam B
AB
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
Hundal
Ripudaman S
RS
Dufour
Sylvie
S
Lebon
Vincent
V
Befroy
Douglas
D
Cline
Gary W
GW
Enocksson
Staffan
S
Inzucchi
Silvio E
SE
Shulman
Gerald I
GI
Petersen
Kitt F
KF
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D002153:Calorimetry, Indirect; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005227:Fatty Acids / Q000097:blood; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008055:Lipids / Q000032:analysis / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D017551:Microdialysis; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects*; D010084:Oxidation-Reduction; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D045162:Thiazolidinediones; D014280:Triglycerides / Q000032:analysis*
D001786:Blood Glucose; D005227:Fatty Acids; D006442:Glycated Hemoglobin; D005990:Glycerol; D007328:Insulin; D008055:Lipids; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides