[PPARgamma and insulin resistance].
The thiazolidinediones (TZD), a new class of oral antidiabetic agent, act by improving insulin sensitivity. TZD correct hyperglycemia and hyperinsulinism in several animal models of NIDDM. Clinical studies in human have confirmed that TZD lowered postprandial and postabsorbtive glycemia and insulinemia. Glucose clamp studies have clearly shown a 30% improvement of insulin-induced glucose utilisation in skeletal muscle. TZD bind to an isoform of a nuclear receptor, the PPARgamma (Peroxisome Proliferator-Activated Receptor). PPARgamma is a transcription factor which, after heterodimerisation with the retinoid receptor (RXR), binds to specific response elements of a number of target genes, and control their transcription. How TZD, with their principal site of action being adipose tissue, can improve glucose metabolism in skeletal muscle? In human, skeletal muscles are responsible for more than 80% of glucose uptake in response to insulin and skeletal muscles contain only a limited amount of PPARgamma! This is the paradox to which we attempt to answer.
Girard
J
J
Endocrinologie et Métabolisme, Faculté de Médecine Cochin, F - 75014 Paris, France.
D000273:Adipose Tissue / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D013844:Thiazoles / Q000627:therapeutic use; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C089946:2,4-thiazolidinedione