Patricia Brubaker

Professor, Departments of Physiology and Medicine
Canada Research Chair (Tier 1) in Vascular and Metabolic Biology

Research Synopsis

Keywords: Intestine/ Pancreas/ Brain/ Peptide Hormones/ Growth Factors/ Diabetes/ Intestinal disease.

Detailed Description: 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 almost 100 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, gastric emptying and appetite. Furthermore, more recent studies have shown that GLP-1 induces pancreatic beta-cell growth, suggesting that it may play a role in the regeneration of pancreatic islets. Because of its pleiotrophic effects to reduce blood sugar levels, GLP-1 receptor agonists and GLP-1 degradation inhibitors have recently been approved as novel treatments for patients with Type II diabetes.

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 has now been so convincingly demonstrated that FDA approval is currently pending for the use of a long-acting GLP-2 analog in patients with Short Bowel Syndrome; phase II trials for patients with Crohn’s disease are also underway.

As a model for studies on the tissue-specific production of regulatory peptides, the proglucagon-derived peptides represent a novel and physiologically important family of hormones. My laboratory utilizes a wide-variety of in vitro, ex vivo and in vivo approaches to investigate the synthesis, secretion and biological activities of these peptides.

METHODS USED

Cell and tissue cultures: Pancreas cells, intestinal cells.

Procedures: Adenovirus, Elisa, pancreas cells, HPLC, gene expression analysis, intestinal cells, immunohistochemistry, immunocytochemistry, microarrays, qRT-PCR, RIA, RT-PCR, signal transduction characterizations, siRNA, western blot, primary cell culture, cell lines.

EQUIPMENT USED

Analytical balances, benchtop centrifuge, blotting apparatus, culture hood, culture incubators, deconvolution fluorescence microscope, departmental beta and gamma counters, dissecting microscope, fluorescence microscope, fresh tissue sectioning systems, gel apparatus, HPLC, infusion apparatus, IVIS whole animal imager low- and high-speed centrifuge, low and ultralow freezers, microwave oven, mini vortexer, plate reader (MesoScale Discovery and others), real-time/thermocycler, setups for electrophoresis, stirrer/hot plate, water baths, IVIS whole animal imager, ultracentrifuge.

PRESENT TRAINEES

Kaori Austin ( Yamada)
Melanie Markovic
Alexandre Martchenko
Bradley Smither
Holly Stacey
Sarah Wheeler
Dr. Stina Jensen

PRESENT COLLABORATIONS

Within the Department of Physiology:
Steffen-Sebastian Bolz
Herbert Gaisano

Outside the Department of Physiology:
Daniel Drucker, University of Toronto
Fiona Gribble, Cambridge, England
Martin Holzenberger, Paris, France
John Pintar, Piscataway, NJ
Sylvie Robine, Paris, France

Recent Publications

Glucagon-Like Peptide-2 Requires a Full Complement of Bmi-1 for Its Proliferative Effects in the Murine Small Intestine. Smither BR, Pang HY, Brubaker PL. Endocrinology. 2016 Jul;157(7):2660-70. doi: 10.1210/en.2016-1127. PMID: 27187177

Short-term sleep deprivation with nocturnal light exposure alters time-dependent glucagon-like peptide-1 and insulin secretion in male volunteers. Gil-Lozano M, Hunter PM, Behan LA, Gladanac B, Casper RF, Brubaker PL.   Am J Physiol Endocrinol Metab. 2016 Jan 1;310(1):E41-50. doi: 10.1152/ajpendo.00298.2015.  PMID: 26530153

Appointments

Cross-appointment: Medicine

Courses

Course Number: PSL304H, PSL305H and PSL1014H
Course Name: