[Insulin-sensitizing agents: metformin and thiazolidinedione derivatives].
Both metformin and thiazolidinedione derivatives(TZDs) improve insulin resistance, a major pathogenesis of type 2 diabetes, and decrease blood glucose levels without stimulating insulin secretion. Metformin inhibits glucose output from the liver, while TZDs increase glucose utilization in the peripheral tissues. In addition, there has been indicated that these agents ameliorate metabolic syndrome beyond glucose-level lowering. Molecular targets of these agents have recently been revealed; AMP-activated protein kinase (AMPK) for metformin and adiponectin, while PPAR gamma for TZDs which induce gene expression of adipocyte glycerol kinase and adiponectin. Insulin-sensitizing agents are clinically useful for obese diabetic patients with insulin resistance. However, periodical examinations are necessary to avoid serious adverse effects such as lactic acidosis, although rare, by metformin and liver injury by TZDs.
Satoh
Jo
J
Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine.
D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D005991:Glycerol Kinase / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D009765:Obesity; D011506:Proteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism
D052242:Adiponectin; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D008687:Metformin; C089946:2,4-thiazolidinedione; D005991:Glycerol Kinase; D017868:Cyclic AMP-Dependent Protein Kinases