Due to the explosive increase in the number of people diagnosed with diabetes world-wide in the past two decades, we can now speak of diabetes epidemic even if this word seems inappropriate in conjunction with a chronic disease. Diabetes is now considered as one of main threats to human health in the 21-st century. It is a metabolic disorder primarily characterized by insulin resistance and elevated blood glucose levels. Insulin resistance and glucose intolerance are key elements of the metabolic syndrome, which is currently associated with impaired function of PPAR gamma nuclear receptor and excessive production of fat tissue hormones. PPAR gamma is critical transcription factor in regulating lipid and glucose metabolism as well as insulin sensitivity, thus PPAR gamma receptor is considered as a very promising molecular target for developing new antidiabetic compounds.

New investigated compound is a phenylpropanoic acid derivative (non-thiazolidinedione), selective, partial agonist of PPAR gamma nuclear receptor. As a partial PPAR gamma agonist, new compound has less than 30% of the activity associated with currently marketed full PPAR gamma agonist, rosiglitazone. Theoretically, our partial agonist should minimize side effects associates with rosiglitazone treatment by limiting the spectrum of activation of PPAR gamma. Consistent with this prediction, animal studies have revealed that the compound is effective in lowering blood glucose levels and demonstrates a relatively benign adverse event profile at putative therapeutic dose ranges. Doses used in animal models of diabetes such as the db/db mouse and the ZDF rat showed significant efficacy in the control of blood glucose level with minimized body weight gain, when compared to rosiglitazone. Moreover safety pharmacology and toxicology studies with mice, rats, dogs and monkeys suggest a broad safety window in which to study new compound’s benefits in humans.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/23156 must be provided.

1. New phenylpropanoic acid derivative with antidiabetic potential acting as a partial PPAR gamma agonist – preclinical studies.
2. SYNTHESIS OF NEW 3-PHENYLPROPIONIC ACID DERIVATIVES HAVING ANTIDIABETIC ACTIVITY
3. PURIFICATION AND ISOLATION OF PPAR LIGANDS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY
4. MODULATION OF TRANSCRIPTIONAL ACTIVITY IN ADIPOSE TISSUE OF db/db MICE AFTER ORAL ADMINISTRATION OF NOVEL POTENTIAL ANTIDIABETIC DRUGS (AD10369, AD10371, AD10797, AD10798 AND AD101025).
5. 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.