The Effects of Recurrent Hypoglycemia on Neural Glucose Sensing Mechanisms

Background

The importance of maintaining good glucose control over a lifetime of diabetes to avoid cardiovascular, renal and neurological complications has been well established by several landmark clinical trials. However, lowering glycemic goals for diabetic patients increases their risk for hypoglycemia ("low blood sugar") exposure. Hence, hypoglycemia is one of the most serious acute complications of insulin-treated diabetes and remains the limiting factor in maintaining proper glycemic control. The brain and in particular, the ventromedial hypothalamus (VMH), plays an important role in detecting when blood glucose levels start to fall and then activates the appropriate hormone responses to correct the decline. However, repeated exposure to hypoglycemia can impair the brain's ability to sense a fall in blood sugar levels. Our laboratory's primary focus centers around understanding how neurons in the brain detect hypoglycemia and coordinates an appropriate hormone response through the release of neurotransmitters. More importantly, we try to understand how recurring exposure to hypoglycemia and diabetes impact these sensing mechanisms and look for potential therapeutic targets that can prevent hypoglycemia. Our lab combines cutting-edge neuroscience and molecular genetic techniques with classic physiology to evaluate brain and peripheral metabolism. If hypoglycemia can be prevented, it will enable physicians to treat diabetes more aggressively and allow patients to achieve more optimal glucose targets, decrease the risk of diabetic complications and improve lifelong outcomes.

Student Role

The students would work on a project examining how recurring exposure to hypoglycemia influence glutamate metabolism in astrocytes. The student will have an opportunity to engage in all aspects of the project from learning about basic biochemistry and neuroscience to performing vascular and stereotaxic surgery and conducting glucose clamp studies. They will have an opportunity to learn molecular techniques that are specific to their projects, including immunohistochemistry, immunoblots and RT-PCR. I will work with the student to develop a project that suits them. In general, undergraduate students initially work alongside one of our senior lab personnel and once they are comfortable, they have the option to work on the project independently. The students will also participate in weekly lab meetings where they present their findings to our research group which helps them develop formal presentation skills. Besides acquiring basic laboratory skills, the students will gain a better understanding of how brain adaptations to hypoglycemia can lead to the development of diabetic complications by the end of the research experience.

Outcomes

Students will acquire basic laboratory skills and will also obtain a better understanding of diabetes and its associated complications. Research in a biomedical laboratory presents students with the opportunity to engage in a number of different life skills stemming from basic literature searches to designing and executing an experiment. Importantly, what the students develop throughout this experience are critical thinking skills that will remain with them for the rest of their lives. Students learn how to apply the knowledge they have gained and they also learn how to critically evaluate the literature they read and their own modes of experimentation. In addition, the students will learn how to write scientific papers and make formal, clear and concise presentations. These are all critical skill sets that serve as a basic foundation and can be applied to one's future career, regardless of the field of study.

Owen Chan
Associate Professor

Internal Medicine
College of Medicine

As their mentor, I generally try to work with the student to identify what their interests are and what motivates them. Together, we develop a project that suits the student's interests and skill level. In general, I try to create a project that will build upon the students' strengths while also helping to improve on their weaker areas. To achieve these goals, I will usually have the student work alongside one of our senior research personnel to help train them in the use of laboratory equipment and with the proper execution of laboratory procedures. Working with senior personnel initially helps to foster a sense of community within the lab and helps the students build confidence in their abilities. As they become more comfortable in the lab, the students usually begin to work more independently as they take ownership of a project. I meet with the students on a weekly basis to discuss the progress of their project and offer advice whenever I can - whether on their research or presentations. In addition, I feel it is important create a laboratory environment where individuals understand that science is challenging and that mistakes will be made but this is acceptable provided these errors are acknowledged honestly and we learn from the mistake. This helps to encourage growth through challenge and mutual respect. I often encourage students to learn by asking questions and create an interactive research environment.