Patricia Brubaker

Dr. Patricia L. Brubaker is a Canadian physiologist, and a professor in the physiology department and department of Medicine at the University of Toronto. Dr. Brubaker's research is focused in endocrinology and the study of diabetes. The major interest of my laboratory is the factors that determine tissue-specific synthesis, secretion and bioactivities of regulatory peptides. In particular, we have focussed on a family of peptides that are produced in the intestine, pancreas and brain, the proglucagon-derived peptides that are encoded by the proglucagon gene. Proglucagon encodes the sequence of at least 9 distinct peptides, including glucagon, and the glucagon-like peptides, GLP-1 and GLP-2. The physiological role of pancreatic glucagon as a stimulator of hepatic glucose production has been known for over 70 years. In contrast, the biological functions of the intestinal proglucagon-derived peptides, GLP-1 and GLP-2, have only been elucidated over the past two decades.

In 1987, it was first established that GLP-1 is a potent stimulator of glucose-dependent insulin secretion. Since then, GLP-1 has also been demonstrated to inhibit glucagon release and gastric emptying, and to reduce both appetite and body weight. Because of its pleiotrophic effects to reduce blood sugar levels and cause weight loss, GLP-1 receptor agonists and GLP-1 degradation inhibitors have been approved as novel treatments for patients with Type II diabetes as well as obesity. Recent studies have also demonstrated a key role for GLP-1 in the regulation of the metabolic circadian clock in response to food intake, suggesting a possible role in the treatment of metabolic diseases associated with circadian disruption, such as in shift workers.

The function of GLP-2 as a stimulator of intestinal growth and function was first demonstrated by Drucker and Brubaker in 1996. The importance of this peptide to intestinal health in both physiology and disease was so convincingly demonstrated that regulatory approval for the use of a long-acting GLP-2 analog in patients with Short Bowel Syndrome was granted in 2012. Studies since that time have focussed on the mechanism of action of this intestinal hormone to stimulate not only intestinal growth, but also nutrient digestion and absorption, as well as barrier function.

My laboratory has utilized a wide-variety of approaches to investigate the synthesis, secretion and biological activities of GLP-1 and GLP-2, including in vitro primary and tumour cell cultures, normal and genetically-manipulated animal models, immunohistochemistry, high performance liquid chromatography, western blot, RT-PCR, real-time PCR, RNAseq and 16S rRNA gene sequencing.