G protein-coupled receptors (GPCRs) constitute a large protein family in human body with the impct on an array of cellular functions, including endocrine hormone secretion. Based on their considerable diversity at the sequence level the GPCRs have been separated into distinct groups of which a vast numbers are expressed by pancreatic islet cells. From a medical point of view we believe that these pharmacologically easily modifiable GPCRs are one of the most important drug targets for the pharmaceutical industry as evidenced by the fact that approximately more than 30% of all marketed drugs act on these receptors.
The aim of my research projecrs is to combine pharmacological tools such as reversed pharmacology with molecular biology approaches (identification of down-stream signaling proteings molecules) to identify the endogen ligand of orphan GPCRs and also to address the possible roles that they might have on pancreatic islet cell function. My GPCR studies have led to a new concept within the field (conjugated receptor system) that certain receptors influence each other´s effect in a positive way concerning β-cell function and to achieve the best effect, we must use combined drug-therapy (dimeric drugs) (see figures). The interaction of GIP-GLP-1 conjugate with the GIPR-GLP1R could be a good example of such dimeric drug hypothesis.
So there is no doubt that the different GPCR systems that we have investigated will be future therapeutic targets for the treatment of obesity and type 2 diabetes.
CRC, Jan Waldenströms gata 35, SUS Malmö
S_albert [dot] salehi [at] med [dot] lu [dot] se