Technologies

Since Protein-Tyrosine Phosphatase 1B (PTP1B), a non-receptor PTP, has emerged as a potential target for the treatment of obesity and type 2 diabetes, a number of academic and industry research laboratories focused on generating PTP1B-specific inhibitors. Currently, the cell-based platforms that could be utilized to test the specificity and efficiency of PTP1B inhibitors are not ideal. They are mostly fibroblast cells that do not respond to insulin appropriately and in a “physiological” manner.

To circumvent these problems, researchers at the University of California, Davis have developed a platform to test the effects of human PTP1B inhibition not only on insulin signaling, but also adipose differentiation and metabolic regulation. Primary brown adipose tissue (BAT) cells were derived from PTP1B knockout (KO) mice, immortalized, then retrovirally-reconstituted with either backbone vector (KO), human wild type PTP1B, “substrate-trapping” mutant PTP1B D181A, and sumoylation-resistant mutant PTP1B K4R. These pre-adipocytes could be induced to differentiate into fat cells enabling one to assess the effect(s) of PTP1B deletion and its mutants on insulin signaling, adipocyte differentiation and metabolic regulation. In addition, the substrate(s) of PTP1B that are mediating these effects could be easily identified.

Platform for testing the effects of human PTP1B inhibition on insulin signaling, adipose differentiation and glucose uptake.