The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes

Diabetes. 2002 Mar;51(3):797-802. doi: 10.2337/diabetes.51.3.797.

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 (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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipose Tissue / metabolism
  • Blood Glucose / metabolism
  • Body Composition
  • Calorimetry, Indirect
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Fatty Acids / blood
  • Glucose Clamp Technique
  • Glycated Hemoglobin / analysis
  • Glycerol / blood
  • Glycerol / metabolism
  • Humans
  • Hyperinsulinism
  • Insulin / blood
  • Insulin / pharmacology*
  • Kinetics
  • Lipids / analysis
  • Lipids / blood
  • Lipolysis / drug effects
  • Liver / chemistry
  • Liver / drug effects*
  • Magnetic Resonance Spectroscopy
  • Microdialysis
  • Middle Aged
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / drug effects*
  • Oxidation-Reduction
  • Rosiglitazone
  • Thiazoles / pharmacology*
  • Thiazoles / therapeutic use
  • Thiazolidinediones*
  • Triglycerides / analysis*

Substances

  • Blood Glucose
  • Fatty Acids
  • Glycated Hemoglobin A
  • Insulin
  • Lipids
  • Thiazoles
  • Thiazolidinediones
  • Triglycerides
  • Rosiglitazone
  • Glycerol