Insulin resistance is characteristic of type 2 diabetes and involves a defect in the body's ability to respond to insulin. In particular, insulin-induced glucose uptake and turnover in skeletal muscles decreases.
Liver X receptor (LXR) is a transcription factor that is important for the turnover of fat and cholesterol in the body. We have shown that LXR agonists increase fatty acid uptake and storage in muscle cells and that glucose uptake and oxidation also increases. Known LXR-activators is a group of endogenous oxysterols (cholesterol metabolites). It is shown in the group that a synthetic oxysterol (22-S-hydroxy cholesterol) may act as an LXR antagonist and can reduce the production of fat and also increase the glucose uptake in skeletal muscle cells.
A method for synthesis of the pharmacophore in 22S-HC has now been established, opening for a short path to new analogues of 22S-HC.
The aim is to identify new substances influencing the gene expression related to lipogenesis and glucose metabolism. It is already identified substances that have biological effects at similar levels as the endogenous substrates.
The project is funded by FORNY (NFR) through Inven2 AS.