Hypoglycemia (low blood sugar) is the most serious acute complication in insulin-treated diabetes and it remains the limiting factor in maintaining proper glycemic control. The brain, and especially the ventromedial hypothalamus (VMH), plays a crucial role in sensing hypoglycemia and initiating the physiological hormone responses to correct it. However, both recurring exposure to hypoglycemia and longstanding diabetes can impair the mechanisms that normally correct the fall in blood glucose levels. Our laboratory utilizes a combination of neuroscience (microdialysis, microinjection, optogenetics), metabolic (glucose clamps), genetic (targeted knockdown or overexpression), molecular biology (qRT-PCR, westerns, immunohistochemistry), and cell culture techniques to identify the neural mechanisms that are involved in the detection of hypoglycemia and understand how these central sensing mechanisms are impaired by recurring exposure to hypoglycemia and in diabetes.
Students will have the opportunity to work alongside one of our research staff to learn techniques in rodent survival surgery and post-operative animal care. They will work closely with members of our research team to perform glucose clamp and microdialysis studies. In addition, they will also have the opportunity to learn various biochemical assays and molecular biology techniques and perform some data analysis.
Student Learning Outcomes and Benefits
Students will gain a basic understanding of diabetes pathology and the complications that arise from insulin treatment. In addition, they will gain a better understanding of the complex brain circuits that are involved in regulating the hormone responses to hypoglycemia and how they are affected by diabetes and exposure to low glucose. In the lab, the students will have an opportunity to learn basic surgical techniques (implanting vascular catheters and some stereotaxic surgeries) as well as how to conduct metabolic clamp studies. Additionally, the students will gain experience in critical thinking and in preparing a scientific presentation.
Dr. Owen Chan is renowned for his research in brain glucose sensing and the central mechanisms involved in the pathophysiology of hypoglycemia unawareness. His laboratory utilizes cutting-edge neuroscience techniques to study neural circuits that participate in the regulation of peripheral glucose metabolism and understand how brain metabolism is impacted by recurring exposure to hypoglycemia and diabetes. His research shows that during hypoglycemia, when glucose supplies become limited, the brain adapts to using other types of fuel substrates besides glucose to meet its metabolic needs. This in turn, prevents the brain from detecting a fall in blood glucose levels, making the patients unaware of the fact that their blood glucose levels are declining. These discoveries have paved the way to developing novel treatment strategies to reduce or prevent hypoglycemia in patients with diabetes.
I believe that students learn best through first-hand experience and working through a problem. In general, I believe that as a mentor, our job is to provide the students with the necessary background and support to conduct their research, but also to provide them with the guidance they need when they encounter obstacles. As mentors, one of the best things we can do is to challenge our trainees to think for themselves and to guide them to the answers they seek and not to give them the answers. I meet with students on a one-to-one basis at least once per week to go over their projects and have them prepare journal clubs to practice speaking in front of an audience. For their final presentations, I review the presentation with the students individually to provide feedback and then have them present it to the lab for critiques.