Thiazolidinediones, such as pioglitazone, are synthetic ligands for peroxis
ome proliferator-activated receptors (PPARs). They after the transcription
of genes influencing carbohydrate and lipid metabolism, resulting in change
d amounts of protein synthesis and, therefore, metabolic changes. Pioglitaz
one improves glycaemic control in people with Type 2 diabetes by improving
insulin sensitivity through its action at PPAR gamma1 and PPAR gamma2, and
affects lipid metabolism through action at PPAR alpha. The results of these
interactions include increases in glucose transporters 1 and 4, lowered fr
ee fatty acids, enhanced insulin signalling, reduced tumour necrosis factor
alpha (TNF alpha) and remodelling of adipose tissue. Together, these can i
ncrease glucose uptake and utilisation in the peripheral organs and decreas
e gluconeogenesis in the liver, thereby reducing insulin resistance.