Peroxisome Proliferator Activated Receptor gamma is a member of the nuclear receptors superfamily of ligand-activated transcription factors that have a central role in the storage and catabolism of fatty acids. PPAR gamma agonists promote adipocyte differentiation and have insulin - sensitizing effects in animal and diabetic patients.

Effects of potential PPAR agonists were tested on mouse type 2 diabetes models. Compounds (library of 8000 molecules designed by Organic Synthesis Laboratory, Adamed Ltd.) were preselected with help of competition binding test with PPAR gamma receptor. Recombinant PPAR gamma Ligand Binding Domain was used in ligand binding assay to determine the ability of subjected chemical compounds (potential PPAR protein ligands) in order to displace radioligand bound to receptor (tritiated reference compound with known strength of binding). Next the ability of these molecules to differentiate of 3T3-L1 cells into mature lipid bearing adipocytes was tested.

Diabetic db/db mice -an animal type 2 diabetes model - were orally administered with 5 chosen molecules: AD10369, AD10371, AD10797, AD10798 and AD101025 capable of both LBD PPAR gamma binding and 3T3-L1 fibroblasts differentiation. After 2 weeks of treatment total RNA was prepared from perigonadal adipose tissue and the expression levels of genes involved in the metabolism of glucose and lipids was determined by comparative real-time PCR. The expression of diabetes-related genes was measured in untreated and drug-treated db/db mice and compared to rosiglitazone treated db/db mice.

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1. New phenylpropanoic acid derivative with antidiabetic potential acting as a partial PPAR gamma agonist – preclinical studies.
2. New phenylpropanoic acid derivative with antidiabetic potential acting as a partial PPAR gamma agonist – preclinical studies.
3. THE COMPARISION OF ACTION OF NOVEL POTENTIAL ANTIDIABETIC DRUGS (AD10 369, AD10 371, AD10 797, AD10 798 AND AD10 1025) ON PLASMA LIPIDS AND GLUCOSE LEVELS IN db/db MICE.