Insulin and glucagon are critical components of metabolic pathways that regulate energy homeostasis in mammals. Dysfunction of these important pathways can result in disease states that are of growing public health concerns, such as diabetes and obesity. Model organisms are increasingly used as tools to gain further understanding of biochemical pathways that are conserved across species. Drosophila melanogaster has found increasing use as a model organism to understand metabolic disease and feeding behavior. Drosophila insulin-like peptides (DILPs) and adipokinetic hormone (AKH) are neuropeptides that have similar roles as mammalian insulin and glucagon, respectively. For example, removal of insulin secretion in a fly results in markedly elevated circulating carbohydrate levels;conversely, removal of AKH secretion results in lowered circulating carbohydrate levels. Several studies have been recently published revealing the importance of the insulin- and glucagon-like signaling pathways in Drosophila in controlling growth, metabolism, and feeding behavior. The primary focus of this proposal is to characterize the expression pattern and functional role of the AKH receptor in Drosophila, the functional homolog of the mammalian glucagon receptor.
Our specific aims are (1) to assess the role of the AKH receptor in mobilizing internal energy stores, (2) to determine the mechanisms by which the AKH receptor modulates food-searching locomotor behavior, and (3) to ascertain the functional role of the Drosophila AKH receptor in taste perception. We will also use a variety of genetic techniques to manipulate the expression of the AKH receptor, as well as generate mutants with altered expression patterns. We will also undertake a detailed characterization of the physiological and behavioral consequences of AKH receptor expression.
We hope that results obtained from our investigations will yield insights into the regulation of energy balance and metabolism that are relevant to human disease. We are particularly interested in biochemical pathways that are involved in conditions that could lead to diabetes or obesity.
