Studying zebrafish pancreases to understand diabetes
Noura Faraj’s family experience encouraged her to pursue a PhD to learn more about type 1 diabetes (T1D). By using zebrafish as a model organism to study the function of the pancreas, she intends to find one probable cause of this condition and, hopefully, help some people to avoid developing T1D in the future.
My name is Noura, which—in Arabic—is the name of a flower. I am from Syria and finished my Pharmacy degree programme there, and I later received a scholarship to follow my Master’s degree programme in Hungary. Not only did receiving this scholarship change my career path, it also—quite literally—saved my life from the war. While being away from my war-torn country, my thoughts were still there when I heard about my 7-year-old cousin. My cousin was recently diagnosed with type 1 diabetes, a condition that has no known cure and, on top of that, lives in a country that is embroiled in civil conflict, which makes it risky to purchase insulin medication. The number of autoimmune disorders has been rising in Syria and it is nearly impossible for patients to receive treatment in the current situation. After obtaining my Master’s degree, I decided to continue studying and do more in-depth research on diabetes since I am both a pharmacist and a human. To do so, I began my PhD study mission in a different country (The Netherlands) in 2020, and a fresh chapter started…
What is Type 1 diabetes?
I joined a research group at the University Medical Center Groningen that focuses on studying type 1 diabetes, or T1D for short. This disease is indicative of the body losing control over blood sugar. The effect is that people with T1D have high blood sugar levels from time to time. Also, T1D patients may suffer from several symptoms: feeling hungry, thirsty, urinating a lot, headaches, tingling limbs, blurry vision, stomach ache, and so on, and the only way to prevent these symptoms from occurring is by administering the optimal dose of insulin. A patient with T1D may be at risk if they lack the ability to adjust their insulin levels due to illness, stress, or excitement. The difference compared to type 2 diabetes is that in type 1 diabetes, the pancreas does not produce insulin because the body attacks itself, whereas in type 2 diabetes, the pancreas makes less insulin and the body is resistant to it. Practically, patients who are diagnosed with T1D constantly have to calculate the appropriate insulin dose depending on their activity and diet and on a daily and moment-by-moment basis. That is a tough daily task, isn’t it? Unfortunately, T1D patients don’t have a choice and are completely dependent on insulin medication, because without it, they will die.
'It might be that damage to the exocrine is the cause of the malfunctioning of the neighbouring beta cells, leading to the body attacking its pancreatic beta cells and ultimately to T1D.' Photo by Henk Veenstra.
Exocrine is a potential trigger
The organ that is ultimately responsible for diabetes is the pancreas. You can find this two-part organ behind the stomach. The larger part of the pancreas is called the exocrine. The exocrine produces proteins called enzymes, which are released into the gut and help with the digestion of food. The smaller part of the pancreas is known as the ‘islet’ and is made up of a collection of diverse cells that produce a variety of hormones. One of these hormones, insulin, regulates blood sugar levels and is produced by cells called beta cells. In patients with type 1 diabetes, these insulin-producing beta cells are damaged because of the body attacking itself. Yet, it is unclear what causes this attack. In my PhD research, I am looking into the interplay between the two parts of the pancreas. More specifically, I would like to find out what effect the bigger part, the exocrine, has on the functioning of the smaller part, beta cells that produce insulin. It might be that damage to the exocrine is the cause of the malfunctioning of the neighbouring beta cells, leading to the body attacking its pancreatic beta cells and ultimately to T1D. In my research, I study the relation between the two parts of the pancreas. But how can we track the communication between the cells of the exocrine and the cells of the islet in a live system?
'Working with zebrafish is also very practical: two-day old zebrafish already have insulin-producing beta cells and their exocrine develops in four to five days after being born.' Photo by Henk Veenstra.
Zebrafish and advanced microscopies
As live monitoring of the communication between the two parts of the pancreas is not possible in humans, we started looking for appropriate model organisms. The most important criteria were that the pancreas of the model system looks like the human pancreas and that the organism is transparent, which is important for live imaging. Zebrafish turned out to be a suitable model for our study since both the form and the function of the human and zebrafish pancreas are similar. Working with zebrafish is also very practical: two-day old zebrafish already have insulin-producing beta cells and their exocrine develops in four to five days after being born. What a role model! Furthermore, zebrafish larvae are small and transparent, which enables us to study their pancreases directly, functioning inside the body as the fish go through various conditions. A microscope can be used to look at the cells in more detail and to see what is happening. More specifically, we can induce damage in the exocrine portion of the zebrafish pancreas and, at the same time, look at the impact of that exocrine damage on beta cells in those zebrafish. In that way, we can find out if there is a relation between the two parts of the pancreas in the development of type 1 diabetes and hopefully gain some more insight into how the body works! Right now, we have been successful in creating several zebrafish lines and optimizing techniques that will provide us with an answer to our main question. Now, that sounds cool, doesn't it?
T1D prevention is another strategy...
Living with type 1 diabetes is very challenging. People with T1D struggle daily to maintain their blood sugar levels within the normal range while exercising and even sleeping. By identifying a probable cause of type 1 diabetes, this research may help some people to avoid developing this condition in the future. By then—hopefully—young children at risk of T1D can enjoy their childhood without T1D.
'By identifying a probable cause of type 1 diabetes, this research may help some people to avoid developing this condition in the future.' Photo by Henk Veenstra.
This article was created in collaboration with RUG Magazine.
Noura Faraj is a PhD student from the UMCG / University of Groningen at the Department of Biomedical Sciences of Cells and Systems.