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 exendin-4, liraglutide, and other 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, intestinal and cardiovascular biology, islet growth, and apoptosis. We are also carrying out studies to 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, 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.