Peroxisome Proliferator-Activated Receptors (PPARs) in Glucose Control

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that control lipid and glucose metabolism. PPARs regulate gene expression by binding with retinoid X receptor as a heterodimeric partner to specific DNA sequences, termed PPAR response elements. In addition, PPARs may modulate gene transcription by directly interfering with other transcription factor pathways in a DNA-binding independent manner. To date, three different PPAR isoforms, designated α, β/δ, and γ, have been identified. PPAR-γ was the first isoform demonstrated to affect carbohydrate metabolism and PPAR-γ agonists, the thiazolidinediones, are now in clinical use for the treatment of insulin resistance. Unexpectedly, later studies revealed that also the other two isoforms modulate glucose metabolism. Here we summarize our understanding on how these nuclear receptor isoforms are involved in the control of glucose metabolism, describing some of the novel regulatory mechanisms. In addition, this chapter reviews the evidence and recent developments relating to the role of some foods containing natural compounds as PPAR agonists.