The effects of glucagon suppression and leptin on diabetes

Currently, 3.4 million Canadians have diabetes. This number is expected to increase by 44% within the next 10 years, raising the number of Canadian diabetic patients to 5 million. Approximately 10% of diabetes cases are type 1 diabetes, for which patients require multiple daily insulin injections. Insulin treatment helps manage type 1 diabetes but this therapy is not perfect as it leads to daily fluctuations in blood glucose levels. Current research by Dr. Timothy Kieffer and PhD student Ursula Neumann aims to create a solution to glucose fluctuations through investigating the relationship between glucagon suppression and leptin. In the summer of 2015, Faculty of Medicine Summer Student Research Program participant Jessica Ho was given the opportunity to participate in this research with Dr. Kieffer and Ursula.

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Jessica Ho (4th year BSc student)

In normal, non-diabetic patients, the hormones insulin and glucagon work together to maintain the body’s blood glucose levels. Insulin is released when blood glucose levels are high. It works by stimulating uptake of glucose into the body’s cells. Glucagon, on the other hand, is released when blood glucose is low. It acts on the liver to release stored glucose from its cells into the blood. However, in diabetic patients, the body is not able to produce enough insulin to maintain normal blood glucose levels. Interestingly, recent research has found that giving leptin to type 1 diabetic mice can normalize glucose levels, suggesting a potential mechanism to control blood glucose levels without insulin.

Despite years of research into leptin therapy in type 1 diabetes, its mechanism of action is still unclear. As part of this FoM SSRP project, Dr. Kieffer and Jessica set out to test the hypothesis that glucagon suppression is required for leptin therapy to be beneficial in controlling blood glucose levels. Their results show that leptin treatment is able to improve both glucose and fat metabolism, while simply muting glucagon receptors can only improve glucose metabolism. This suggests that glucagon suppression by leptin can only account for some but not all of the metabolic benefits of leptin.

Jessica first became interested in research as a high school student. She began pursuing her research career by working in a yeast epigenetics lab at the UBC Centre for Molecular Medicine and Therapeutics. Jessica held the central role in this project with Dr. Kieffer, and was the primary person performing the experimental work. During this research opportunity, Jessica was involved in blood glucose monitoring and blood collection, assisting with pump implantation, and performing oral glucose tolerance tests and tissue collection. This experience has taught Jessica many skills in the process of conducting effective research, and has inspired Jessica to pursue the study of medicine and research into the causes of human diseases. Jessica presented these findings at the 2015 Vancouver Diabetes Research Day, and is currently furthering her research career with an internship at the World Health Organization in Switzerland.