Pioglitazone: mechanism of action.
Thiazolidinediones, such as pioglitazone, are synthetic ligands for peroxisome proliferator-activated receptors (PPARs). They alter the transcription of genes influencing carbohydrate and lipid metabolism, resulting in changed amounts of protein synthesis and, therefore, metabolic changes. Pioglitazone improves glycaemic control in people with Type 2 diabetes by improving insulin sensitivity through its action at PPAR gamma 1 and PPAR gamma 2, and affects lipid metabolism through action at PPAR alpha. The results of these interactions include increases in glucose transporters 1 and 4, lowered free fatty acids, enhanced insulin signalling, reduced tumour necrosis factor alpha (TNF alpha) and remodelling of adipose tissue. Together, these can increase glucose uptake and utilisation in the peripheral organs and decrease gluconeogenesis in the liver, thereby reducing insulin resistance.
Smith
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Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Göteborg University, Sweden.
D001786:Blood Glucose / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D009687:Nuclear Proteins / Q000187:drug effects; D000077205:Pioglitazone; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077205:Pioglitazone