2021 Virtual Undergraduate Research Symposium
2021 Virtual Undergraduate Research Symposium
Mechanisms of Beta-Cell Death in Type 1 Diabetes
Mechanisms of Beta-Cell Death in Type 1 Diabetes
PROJECT NUMBER: 8 | AUTHOR: Drake Hampton, Chemical and Biological Engineering
MENTOR: Nikki Farnsworth, Chemical and Biological Engineering
ABSTRACT
Type 1 diabetes (T1D) is characterized by a progressive loss of insulin-producing β-cells in pancreatic islets. The immune destruction of β-cells is partly mediated by high levels of pro-inflammatory cytokines. In vitro, cytokines decrease connexin36 (Cx36) gap junction coupling, leading to altered β-cell Ca2+ signaling and insulin secretion. We have shown that pro-inflammatory cytokines alter islet function via protein kinase C δ (PKCδ) dependent mechanisms. Previous studies have suggested a role for PKCδ in mediating β-cell death, however little is known about the role of PKCδ in T1D. The goal of this study was to determine if levels of Cx36 and PKCδ are altered in islets from individuals with T1D. We hypothesize that levels of Cx36 are decreased and levels of PKCδ are increased in islets from patients with T1D compared to healthy controls. To test this hypothesis, we fluorescently labeled insulin, Cx36, and PKCδ in slices of pancreas from T1D or healthy individuals using immunohistochemistry. We developed a MATLAB code to determine the levels of Cx36 and PKCδ in insulin positive cells from fluorescent images of pancreas sections. The results from this project will help to identify a role for changes in Cx36 and PKCδ in the development of T1D. Future studies will correlate changes in PKCδ to immune cell location and β-cell death in the islet to confirm the role of PKCδ in mediating β-cell death in T1D.
PRESENTATION
AUTHOR BIOGRAPHY
I am currently a Sophomore majoring in Chemical Engineering. I am from Highlands Ranch, Colorado, and am also on Mines Activities Council (MAC), which is the sole student-led programming board on campus. MAC plans E-Days, Homecoming, football game tailgates, Oktoberfest, block parties, as well as other events throughout the semester. I like to swim bike and run (triathlon), climb, ski, and I also like to spend time in nature. I am also involved in Kappa Sigma on campus. Over the summers I usually coach youth track and cross country for ages 5-14 and I also work at the bar/kitchen at a golf course in Highlands Ranch. When I was 4 years old, I wanted to be a trash truck driver. I think that what interested me so much about being a trash truck driver was that the trash truck seemed like a very large and complicated piece of machinery. As I have grown up and learned more about the world, I have started to realize how amazing things other than trash trucks can be. I find the chemical engineering curriculum very exciting and I would say that it is a similar appreciation to my four-year-old self’s appreciation for trash trucks. Someday I hope to apply my excitement for understanding how things work to a career that helps people.
Assuming your hypothesis is true, what are the broad implications of this research?
Hi Shaked, the implications of this research, assuming my hypothesis is true, are that decreases in islet electrical coupling occur in type 1 diabetes (T1D) and that PKCdelta plays a role in regulating this dysfunction. A better understanding of the mechanism by which beta-cells die in T1D will hopefully lead to better therapies in the future.
This is very interesting research, and seems like it has the potential to be very impactful! Are you planning to continue working on this project in the future, and will the work continue to combine laboratory work, such as work with cells, as well as more computer based work like the MATLAB you mentioned?
Hi Sydney! Thank you so much! I do plan to continue working on this project with both laboratory work as well as computer-based work like MATLAB. Right now I am working on TUNEL staining, which will show areas of cell death in the islet.
Nice presentation! Good job Drake!
Thank you Meg!
Great job, Drake! So proud of your awesome research and work in the lab.
Thank you Chelsea!
Solid 11/10, nice job bud!
Thanks Jill – wouldn’t have been possible with all your help 🙂
Very interesting project, Drake! Would you expect PKCdelta levels to change with time since disease onset?
Hi Cecilia, thank you! We would expect PKCdelta to peak with the peak in beta cell death, and then decrease as the disease reaches a steady state with no beta cells.
Great job Drake! I thought this was a very interesting project with some very cool images.