Angeles Olvera, Zuraya Elisa
PhD Student
Vincent Poitout, Université de Montréal

Mechanisms controlling beta cell proliferation by nutrients

Beta cells located within the pancreas are responsible for the production and secretion of insulin. T1D is caused by the destruction of beta cells by the body’s own immune response, whereas type 2 diabetes involves eventual loss of beta cell function. This research will examine how oleate (a fatty acid naturally occurring in animal and vegetable fats and oils) contributes to increasing the growth of beta cells. Specifically, the relationship between reactive oxidative species and antioxidant enzymes produced by the beta cells will be examined to determine its role in beta cell proliferation.

Wang, Yufeng 
PhD Student 
Jonathan Rocheleau, University of Toronto

Design of an islet-on-a-chip device to dynamically measure 1st-phase oxygen consumption rate and insulin secretion from individual islets 

The measurement of insulin secretion and oxygen consumption rate by islets is important for characterizing glucose metabolism in people with diabetes. This research project will design an “islet-on-a-chip” – that is, a living islet stabilized inside a microfluidic chip – for the purpose of measuring insulin secretion and oxygen consumption from individual islets simultaneously. These devices will then be used to evaluate the impact of metabolic stresses on islets during glucose metabolism, providing new information about islet cell molecular function. 

Kar, Saumadritaa 
PhD Student 
Bruce Verchere, University of British Columbia 

Mitigating amyloid associated islet transplant failure with pramlintide-expressing human embryonic stem cell derived beta cells 

Transplantation of insulin-producing beta cells is a potential curative therapy for T1D; however, limited organ donors, the need for lifelong immune suppression, and the eventual failure of transplanted cells hinder widespread clinical implementation. One cause of islet transplant failure is the formation of toxic protein aggregates called amyloid. Therefore, this research will examine the use of beta cells from genetically engineered embryonic stem cells. Specifically, these cells will be engineered to produce Pramlintide, which does not form amyloid, and assessed to determine whether the inhibition of amyloid formation could enhance transplant survival and function. 

Velghe, Jane
PhD Student
Bruce Verchere, University of British Columbia

Characterizing human islet-resident macrophages in health and disease

Macrophages are innate immune cells that can alter their function based on their surrounding environment. In mice pancreas, islet macrophages play an important role in development and proliferation of insulin-producing beta cells, and thus are a potential target for diabetes therapy. This research project will analyze human islet macrophages to provide new insight into their function in T1D as well as the communication between macrophages and beta cells. 

He, Siyi 
PhD Student 
Gareth Lim, University of Montreal/CRCHUM

Development of a screening approach to repurpose previously approved drugs to ameliorate Type I Diabetes

Autoreactive CD8+ T cells are the cells responsible for the selective destruction of insulin-producing beta cells in T1D. The survival of CD8+ T cells is controlled through specific protein-protein interactions. This research will identify compounds that can disrupt these protein-protein interactions – leading to destruction of the harmful CD8+ T cells. Small molecules that have destructive effects on CD8+ T cells may be a promising therapy for the delay or prevention of T1D with the additional benefits from small molecule drugs such as oral administration and lower cost as compared to existing therapies that target T cells. 

Hoffman, Emily 
PhD Student 
Michael Riddell, York University 

The role of somatostatin in the deficient glucagon response to acute and recurrent hypoglycemia  

Glucagon is a pancreatic hormone that stimulates the liver to release stored glucose in response to low blood glucose levels as a counter-regulator to insulin, meaning that these two hormones work together to balance blood sugar. Somatostatin inhibits the release of insulin and glucagon, thus, blocking the action of somatostatin may help to prevent hypoglycemia in people with diabetes. ZT-01 is one such drug that acts in this way (i.e., a somatostatin receptor antagonist) and is now being tested in clinical trials for its ability to prevent lows in people with T1D by Canadian company Zucara Therapeutics. This project will delve further into the pathways affected by ZT-01 by studying somatostatin at low glucose levels in rodent models of type 2 diabetes, which will in turn help to inform and advance the ZT-01 development program.

Huang, Hui 
Postdoctoral Fellow 
Jean Buteau, University of Alberta 

A novel small-molecule activator of Lyn kinase for the treatment of type 1 diabetes

Although people living with T1D have a substantial >80% loss of insulin-producing beta cell mass, there is evidence that most people with long-duration T1D still have surviving beta cells and secrete small amounts of insulin. Therefore, approaches that preserve residual beta cells and stimulate beta cell expansion may be a promising therapy for T1D. This research will examine a small molecule activator of Lyn – a novel regulator of beta cell “health”. Through pharmacological activation of Lyn, it is hypothesized that surviving beta cells will be preserved, and beta cell mass expansion will be promoted. This research will have significant implications for clinical therapies to harness existing insulin-producing beta cells in T1D.