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Investigating cytoprotective roles of intracellular C3 in cytokine induced death of pancreatic cells in Type 2 Diabetes

Mckay, Marina (2021) MOBN02 20202
Degree Projects in Molecular Biology
Popular Abstract
A spoon full of insulin helps blood sugar go down

Glucose is the primary source of fuel our bodies extract from carbohydrates to power our cells. Once glucose is released into the blood stream, pancreas reacts by releasing insulin into the blood stream. Insulin is a hormone which allows cells to uptake glucose after a meal. However, when insulin is not produced by the pancreas, or the cells don’t react to available insulin, glucose accumulates in the blood stream. Metabolic disease caused by inappropriate regulation of blood sugar is called Diabetes Mellitus. It is characterized by complications such as tissue damage caused by an excess of glucose and consecutive inflammation.

There are two types of diabetes, type 1 and type 2. Less... (More)
A spoon full of insulin helps blood sugar go down

Glucose is the primary source of fuel our bodies extract from carbohydrates to power our cells. Once glucose is released into the blood stream, pancreas reacts by releasing insulin into the blood stream. Insulin is a hormone which allows cells to uptake glucose after a meal. However, when insulin is not produced by the pancreas, or the cells don’t react to available insulin, glucose accumulates in the blood stream. Metabolic disease caused by inappropriate regulation of blood sugar is called Diabetes Mellitus. It is characterized by complications such as tissue damage caused by an excess of glucose and consecutive inflammation.

There are two types of diabetes, type 1 and type 2. Less common type 1 (T1D) usually has much earlier offset in life and is autoimmune in nature. Patients with T1D are deficient in insulin. Type 2 diabetes (T2D) occurs later in life and is linked to obesity and sedimentary lifestyle. Patients suffering from T2D are resistant to insulin and are also deficient in it. Although for different reasons, common for both types of diabetes is damage to insulin producing β cells caused by systemic inflammation. In our research we study an innate defence mechanism called the complement system which protects pancreatic cells from tissue damage in T2D.

Complement is a large protein system that patrols the body searching for causes of inflammation. When complement binds its target, the central component C3 becomes activated. In T2D, C3 can protect pancreatic cells from damage caused by cytokines by yet to be discovered mechanisms. Cytokines are small, locally produced molecular messengers that navigate immune signalling. Unfortunately, systematic inflammation in the organism leads to excessive amounts of cytokines to be produced during both T1D and T2D.

Can intracellular C3 be the future of diabetes treatment?
Typically, C3 protein is secreted outside of the pancreatic cell. Every protein that is destined to be secreted contains a small peptide sequence which acts as a zip code. This zip code navigates protein to its final destination. However, we observed in pancreatic β cells an additional form of C3 protein which is strictly intracellular. It lacks the zip code and as such is confined to the cytosol of pancreatic β cell.

We exposed pancreatic β cells to cytokines to simulate T2D-like inflammation. We observed cells with cytosolic C3 to have much higher survival rate in comparison to cells that don’t produce it. Therefore, we suspect that the cytosolic form of C3 protein is responsible for the survival of pancreatic cells. Our next step is to understand mode of action of cytosolic C3 in providing protection to pancreatic cells from an excessive cytokine exposure. Hopefully understanding this mechanism would get us closer to finding a non-invasive long-term solution for type 2 diabetes treatment.

Master’s Degree Project Molecular Biology, 45 credits 2021.
Department of Biology, Lund University

Advisor: Ben C. King, PhD.
Protein chemistry/Department of translational medicine, Lund University (Less)
Please use this url to cite or link to this publication:
author
Mckay, Marina
supervisor
organization
course
MOBN02 20202
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9069172
date added to LUP
2021-12-16 12:29:20
date last changed
2021-12-16 12:29:20
@misc{9069172,
  author       = {{Mckay, Marina}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Investigating cytoprotective roles of intracellular C3 in cytokine induced death of pancreatic cells in Type 2 Diabetes}},
  year         = {{2021}},
}