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lüll Peroxisome proliferator-activated receptor translational research and clinical experience Cheatham WWAm J Clin Nutr 2010[Jan]; 91 (1): 262S-266SSince the early 1970s, pharmaceutical biochemists have sought to exploit the scientific findings that were uncovered when they studied the basis for the function and mode of action of fibric acid derivatives. In the early 1970s, little was known of peroxisome proliferator-activated receptors (PPARs), even in concept. Since then, however, the development of bioactive small molecules in medicinal science has resulted in tools developed to be inserted into the PPAR-binding domain, which has resulted in the recognition of literally thousands of possible biological effects of binding configurations. In diabetes care, the first of the marketed agents from these discoveries and developments was introduced in 1996. It was potent and did its job well. However, the use of this early form of thiazolidinedione sometimes, although rarely, led to fulminant liver failure, and ultimately the drug was removed from the market. Subsequent thiazolidinediones have been developed, and 2 have been relatively successful. However, they are not without their problems. This article describes the history of the development of these drugs, identifies the valuable attributes that they possess, and gives a clear rationale as to why a quest for a "safer" PPAR agonist is still being sought.|Adipose Tissue/drug effects/physiology[MESH]|Animals[MESH]|Atherosclerosis/prevention & control[MESH]|Binding Sites[MESH]|Diabetes Mellitus, Type 2/physiopathology[MESH]|Glucose/metabolism[MESH]|Humans[MESH]|Inflammation/prevention & control[MESH]|Insulin Resistance[MESH]|Insulin Secretion[MESH]|Insulin/metabolism/therapeutic use[MESH]|Lipids/physiology[MESH]|Liver/drug effects/physiology[MESH]|Muscle, Skeletal/drug effects/physiology[MESH]|Overweight/physiopathology[MESH]|PPAR gamma/physiology[MESH]|Peroxisome Proliferator-Activated Receptors/*physiology[MESH]|Thiazolidinediones/therapeutic use[MESH]|Translational Research, Biomedical/*methods/trends[MESH] |