SPUR 2021: Neural Mechanisms Involved in Hypoglycemia Sensing

Background

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.

Student Role

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 & Benefits

Students will gain a basic understanding of diabetes pathology and about 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.

Remote Contingency Plan

COVID-19 has presented a tremendous challenge to students, educators and researchers alike. The research environment has had to adapt to the fluidity of the situation, and be able to move from basic bench work to remote research and data analysis in a short period. To accommodate these changes, our laboratory is working to acquire and bank both preclinical and some clinical data, so that data analysis can be performed if the need to work remotely arises. Students who participate in these undergraduate research programs can analyze data remotely as part of their training if they have to work remotely. Additionally, students will have the opportunity to watch surgeries and procedures remotely through interactive video streaming to gain a better understanding of the laboratory procedures that generated the data. In addition, the students will continue to participate in remote lab meetings and journal clubs where the will gain a better understanding of how to prepare and present a scientific presentation.

As we will continue with the basic animal research, the project as described above will remain the same. Alternatively, we are also conducting a study looking at the impact of COVID-19 in diabetic patients. For this particular project, acquired plasma samples from COVID-19 patients are analyzed for the expression of specific genes that may increase the susceptibility of poorly-controlled diabetic patients to complications from SARS-CoV-2 infection.

Owen Chan
Associate Professor

Internal Medicine
School of Medicine

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.