The GPCR Action Group
PI: Albert Salehi
The antiology of metabolic syndrome and type 2 diabetes is complex and involves the interaction between both genetic and environmental factors (also including nutritional and metabolic signals). It has been known for at long time that dysfunction fo pancreatic islets cell (α-, β- and δ-cell) is a critical factor in the development and progression of these diseases.
One of the largest and most diverse protein families of transmembrane receptors, found in human genome is the G-protein coupled receptor (GPCR) superfamily also known as heptahelical receptors, serpentine receptor. The GPCRs play important roles in a wide variety of physiological and pathophysiological processes such as development and proliferation, metabolic disorders, type 2 diabetes, inflammation and angiogenesis to name a few. The ability of the GPCRs to mediate specific signals over cellular and organellar membranes makes them attractive target protein families in pharmaceuticals research and not surprisingly, almost 30% of the top-selling drugs in the market target these GPCRs. However, many of the GPCRs are still "orphan" wigh uncharacterized function.
The aim of research work in GPCR action group will thus be to identify and characterize all GPCRs (including the previously unknown orphan GPCRs) expressed in human pancreatic islets, muscle and fat tissues. Following identification of GPCRs in human tisssue we will continue to identify the natural ligands by different approaches i.e. reversed pharmacology in combination with manipulation of the searched receptor in suitable animal models. Moreover, regarding pancreatic islet cells we will also examine the cellular events coupling the activation of these receptors to ilset cell survival and function. GPCRs have been shown to be major players in various physiologic and pathophysiologic processes. However, they have not been extensively studied in the context of type 2 diabetes and more so in insulin target tissues. We already have generated sufficient and novel background knowledge in this context that would serve as a basis for further characterization.
The research in this action group will not only enhance our knowledge about GPCRs but also hopefully clarify their role in the physiological and pathophysiological events leading to pancreatic β-cell dysfunction as well as development of insulin resistance in the peripheral insulin sensitive tissues.
For more information contact S_albert [dot] salehi [at] med [dot] lu [dot] se (Albert Saleh)i