Research in the Drucker lab is focused on understanding the biology of the glucagon-like peptides. Specific projects include physiological analyses of GLP-1 and GLP-2 action, understanding the biology of glucagon action, and elucidation of the functional control of GLP-1, GIP, and GLP-2 action through studies of their respective receptors.
Students and research fellows utilize a combination of techniques that involve cell culture, studies of signal transduction, cell proliferation and apoptosis, with a major emphasis on generation and phenotypic analysis of mice with disruption of gut hormone action. The lab employs rodent models to delineate novel physiological concepts of gut hormone and glucagon-like peptide action with a focus on potential therapeutic relevance to diabetes and intestinal disease.
The lab maintains an active research interest in studying multiple aspects of GLP-1 action, including the GLP-1-regulated control of glucose homeostasis, and the role of GLP-1 signaling in the central nervous system and heart. These studies employ cell lines, normal rodents, transgenic mice that over-express GLP-1 analogues, and mice with disrupted GLP-1 receptor signaling. The lab is also interested in studying the biology of GLP-1R agonists. The lab uses a combination of approaches to delineate the pharmacological and physiological actions of GLP-1 including analyses of Glp1r-/- mice to understand the importance of GLP-1 for glucoregulation, intestina, nervous system, immunel and cardiovascular biology. We are also carrying out studies to delete or rescue GLP-1 receptor function in specific murine tissues via a transgenic approach in vivo.
Given the biological importance of the incretin hormone GIP, the lab is also studing the role of the GIP in different tissues, from the immune system to the brain, using Gipr-/- mice, and genetic approaches for understanding GIP action in different tissues.
The lab is using mouse genetics and both gain and loss of function experiments to understand the role of GLP-2 in vivo. Current projects include studies of GLP-2 receptor signaling, and studies of both gain and loss of GLP-2 receptor signaling in vivo. The lab employs rodent models of intestinal disease to identify potential therapeutic actions of GLP-2 in vivo. A major focus of the lab is to understand the mechanisms of GLP-2 action by analysis of the downstream targets of GLP-2 in vivo.
The lab continues to focus on studies directed at understanding the physiology of glucagon action and wherever possible uses mouse models to complement data obtained from cell-based studies in vitro. More recent studies are focused on analysis of tissue-specific control of glucagon receptor action using genetically engineered mice, as exemplified by Gcgr-/- mice..
Dipeptidyl peptidase-4 (DPP-4)
Given the importance of this key peptidase in the control of both GLP-1 and GLP-2 degradation, and its role as a key target for diabetes therapeutics, the laboratory is interested in the biology of DPP-4, and its importance, in key tissues and compartments, in the control of multiple metabolic functions.
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