Contact info: Anna Wendt, anna.wendt@med.lu.se
LU research profile: https://portal.research.lu.se/en/persons/anna-wendt
Start date: Any time between September 2025 and January 2026 (can be discussed)
Length of the project: 45 credits
Project type: master project
Additional information: This project is in collaboration with Jens Largerstedt who will be co supervisor. Link: https://portal.research.lu.se/sv/persons/jens-lagerstedt
Project information:
Aim: The aim of this project is to investigate factors that could regulate the levels of the fatty acid transporter CD36 in insulin producing beta cells.
Hypothesis: We hypothesize that the levels of CD36 in beta cells is regulated by several signals that are strong in obesity and type-2 diabetes such as cytokines (IL4 and IL10) and hyperglycaemia, but also other factors such as microRNAs and medication (dexomethazone). We believe this regulation has an impact on type 2 development especially in obese individuals.
Introduction: Obesity is a strong risk factors for developing type-2 diabetes. There are several mechanisms behind this including the fact that in obese individuals, lipids can accumulate in ectopic tissues such as the liver and skeletal muscles. Type-2 diabetes is the result of both increased insulin resistance and dysfunctional insulin secretion, where ectopic lipid accumulation is a known contributor to insulin resistance. Interestingly, lipids can also wrongfully accumulate in insulin secreting beta cells in the islets causing dysfunctional insulin secretion and even cell death in these cells. We have previously shown that fatty acid transporter CD36 levels are increased in islets from obese individuals with type 2 diabetes. We have also shown that reducing the amount of functional CD36 in the beta cells increase insulin secretion. CD36 is expressed in several tissues in the body and the literature tells us that physiologically, CD36 expression is regulated by different mechanisms in different cell types. In this project we will investigate how CD36 is regulated in the beta cells investigating factors suggested by the literature and our previous studies to be important in CD36 regulation.
Project plan: The experiments in this project will mainly be carried out in the human beta cell line EndoC betaH1 which, like human islets, express CD36.
In our group we have extensive knowledge in investigating microRNA regulation of various proteins. MicroRNAs are short non-coding stretches of RNA that negatively regulate protein expression and thereby play an important role in shaping beta cell function. There are several microRNAs that have been shown to regulate CD36 in other tissues but microRNA regulation of CD36 in beta cells has not been investigated. There are data sets available describing the specific microRNAs expressed in beta cells. As a first step we will cross reference these data sets with known and predicted CD36 specific microRNAs. Candidates from this search will be experimentally tested by overexpressing or downregulating the microRNA in the beta cell line. The effects on CD36 expression can then be determined using qPCR and western blot. To better understand the role of the selected microRNAs we will also investigate the effect of these microRNAs on insulin production and secretion using ELISA.
Depending on the findings and on how much time is left we have the possibility to also investigate how cytokines and pharmaceutical compounds affect CD36 expression. IL-4 is a cytokine that regulates CD36 levels in monocytes. We have previously investigated the role of IL-4 on insulin secretion, but we did not look at the effects on CD36 expression. We still have RNA samples from that study that can be used to investigate CD36 levels in the different treatment groups. Similarly, dexamethasone, a commonly prescribed corticosteroid associated with steroid-induce diabetes, has been linked to CD36 expression. Dexamethasone, again, has been investigated in our group but not in association with CD 36 expression.
Significance: It has been estimated that > 6% of the world’s population live with type-2 diabetes and the numbers continue to rise. One major risk factor for the disease is obesity and it is vital to understand the mechanisms behind obesity-driven type-2 diabetes. This project would help us understand the regulation of lipid influx into the beta cells in health and disease, a knowledge that could be used to treat or, hopefully, prevent beta cell dysfunction in type-2 diabetes.