Abstract

Type 2 Diabetes (T2D) is a global healthcare challenge, however very few available treatments address its underlying insulin resistance pathology. Chronic low-level inflammation in adipose tissue is an important hallmark of the T2D, directly contributing to this insulin resistance. Development of insulin-sensitising therapeutics has proved to be challenging due to the limited complexity of current in vitro models and their inability to properly replicate interactions between metabolism and inflammation. We aim to develop a novel 3D model of adipose tissue that better reproduces the cellular microenvironment of T2D adipose. To make this model suitable for compound screening, we will incorporate genetically encoded NanoBiT biosensors. As an initial proof of principle, we are developing biosensors to measure function of the FFA4 free fatty acid receptor, a G protein coupled receptor with a reported role regulating insulin resistance. To date, we have used SGBS cells to generate and characterise human adipocyte spheroids and have designed and tested three classes of NanoBiT biosensor to measure FFA4 function. In this talk, I will discuss the challenges involved in developing a novel in vitro 3D assay alongside the opportunities this platform may bring for early-stage drug discovery.