Author Archives: Chumba Koech

The Role of Glucagon in Insulin Secretion

Glucagon and Insulin are products of the alpha and beta cell respectively, that are essential to maintaining glucose homeostasis. It’s also known that incretins, signaling hormones secreted in our small intestine are essential insulin secretagogues. In understanding ways to mediate insulin production in the beta cell, more must be known specifically about the relationship between glucagon and the glucagon like peptide (GLP-1).  In hypoglycemia conditions glucagon is secreted to increase blood glucose concentrations, whereas in hyperglycemia conditions GLP-1 stimulates insulin secretion to reduce blood glucose concentrations.  In this study, we examined the relationship between glucagon and GLP-1 because we hypothesize that glucagon and GLP-1 work together to increase insulin secretion.  We examined this relationship by performing glucose tolerance tests on our beta cell glucagon receptor knockout mice model(GCGR), to understand the response between glucagon and the beta cell. Then we inhibited the GLP-1 receptor to further understand the relationship between glucagon and GLP-1. We used a Perifusion machine to examine the relationship between the mice’s insulin response specifically in the beta cell to different buffers. If glucagon and the GLP-1 receptor support our hypothesis, future work can be dedicated to creating new agonists that could improve treatment for type 2 diabetic individuals.

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My day in the lab I must say varies a lot day to day. Most weeks we perform several Glucose tolerance tests with our mice, so the morning is spent fasting them and getting prepped for the GTT. This involves me making our glucose that we inject either intraperitoneally or with an oral gavage. After this I label tubes that we use to collect blood samples from. Then we usually have lunch and then go to the mice house later that afternoon to complete our GTT. Then finally after that I take our samples back to the lab, centrifuge them and pipette out plasma to store in our -80 C freezers.

If we aren’t performing GTT’s that day we’re usually, removing islets, and using the Perfiusion Machine to test our islets!  The Perfiusion Machine lets us take our islets from our mice and examine their insulin secretion. The machine is interesting but involves close examination so usually we don’t leave its side.

Perifusion Machine!

In down time, I usually get to help others in the lab with prepping to use the Perfiusion machine, genotyping animals, or general mice handling activities to make them more comfortable.

My lab is always cold but otherwise very comfortable! The office areas of the lab are beautiful since its a converted tobacco drying warehouse.  Since we’re in the heart of downtown Durham there’s always good coffee spots nearby!

Downtown Durham!

The overall theme of my lab concerns looking at the pathways of insulin secretion so that we can better understand type 2 diabetes. One of my post doc focuses for her project involves the relationship between GLP-1 and GIP. In previous studies done at the DMPI, data has suggested that there is a compensatory effect when cognate G-protein coupled receptor (GCCR) was eliminated, leading to an increase for alpha cell GLP-1 content. This information is important for future studies because GLP-1 levels are important for insulin secretion and glucose tolerance.

Right now, our lab is focusing on knocking out different mechanisms in that pathway, for example dipeptidyl peptidase (DPP-4), glucagon-like-peptide-1 (GLP-1), and gastric inhibitory peptide (GIP) to try to understand the critical keys in the pathway for insulin secretion. We’re using different strands of mice to knockout these genes. From these mice, we perform different tests to determine insulin secretion levels. Our main test are glucose tolerance tests and our second test involves using a Perfiusion machine. This machine allows us to measure insulin secretion in islet cells we obtain from our mice. From here we hope to better understand the pathway to insulin secretion, to better aid type 2 diabetic individuals.

Dr. Megan Capozzi is a new face to the Duke Molecular Physiology Institute, where she is a post-doctoral researcher in Dr. Campbell’s lab. This lab focuses on the hormones used in the regulation of insulin secretion and glucose tolerance in type 2 diabetes. This lab uses mice models in their research.

Before Dr. Capozzi arrived at the DMPI, she spent her undergraduate years at Vanderbilt University where she majored in neuroscience. During her undergraduate years, she became involved in research, which lead her to continue her education at graduate school. Throughout her undergraduate years, her main goal was to learn the most she could from all different areas of education. She then continued at Vanderbilt for graduate school where she focused on diabetic retinopathy.

From my few weeks at the DMPI, I’ve been lucky with the people I get to learn from. The members of this lab are collaborative with each other and are great team players. While Dr. Capozzi hasn’t taught in a classroom yet, she enjoys that when you teach others it allows her to think about her own work in another context.

Dr. Capozzi’s favorite part about science is that you get to do something different every day. She also enjoys getting to be the first person to see and interpret her own data daily.

At the end of our interview Dr. Capozzi gave some helpful advice and insight for the future of my academic career. She emphasized on not being afraid of making mistakes because you learn a lot from them. She also advised to try everything I can because I’ll learn more. This information struck me as very important because it helps maximize our opportunities and experiences while at Duke.

The first day I met Dr. D’Alessio and his lab, excitement ensued. I was presented with an opportunity to be engage and learn from a great lab! I was really excited for this opportunity because I had no previous research experience and the summer is a great time to get started. What also made the Duke Molecular Physiology Institute a good fit was everyone’s openness to teach me about research.

When choosing  a lab this I think the first thing that comes to mind is finding a good fit. Ultimately you want to feel a part of the lab, engaged in your daily tasks, and become more informed about the content of your lab. I would say that is what I expect from my summer research experience. I hope to make relationships with these scientists. From learning about their background, interests, and learning the ropes from them.  I can’t wait to successfully aid in glucose tolerance testing and have almost nonexistent error bars.  I expect myself to become more comfortable with the literature out there regarding what my lab is working on.

I also hope to learn more insight about the life of a scientist. Lots of the individuals at the DMPI are at different stages of their academic career: from undergrads like me, to post docs, MD’s, and MD-PHD’s. I expect this summer to  solidify to me future academic pursuits. I also expect through this summer to develop new friendships through BSURF and become an expert bike commuter!

Prepping for the islet cells!