Role of Apolipoprotein A-I in the regulation of insulin secretion from pancreatic beta cells
(2021) MOBN02 20202Degree Projects in Molecular Biology
- Abstract
- High density lipoprotein (HDL) and its principal protein component Apolipoprotein A-I (ApoA-I) are commonly recognised for their anti-cardiovascular disease properties. Multiple studies have indicated that they also have important roles in the context of glycaemic control and diabetes. Low levels of HDL and ApoA-I have been linked to increased risk of diabetes development. Furthermore, it has been shown that HDL and ApoA-I have the ability to reduce plasma glucose and increase insulin secretion. This beneficial effect on glucose metabolism gives them therapeutic potential. Our group previously showed that preincubation with ApoA-I enhances insulin secretion in a beta cell line. The main goal of this thesis was to explain the biological... (More)
- High density lipoprotein (HDL) and its principal protein component Apolipoprotein A-I (ApoA-I) are commonly recognised for their anti-cardiovascular disease properties. Multiple studies have indicated that they also have important roles in the context of glycaemic control and diabetes. Low levels of HDL and ApoA-I have been linked to increased risk of diabetes development. Furthermore, it has been shown that HDL and ApoA-I have the ability to reduce plasma glucose and increase insulin secretion. This beneficial effect on glucose metabolism gives them therapeutic potential. Our group previously showed that preincubation with ApoA-I enhances insulin secretion in a beta cell line. The main goal of this thesis was to explain the biological mechanism behind this process and different steps of glucose stimulated insulin secretion pathway were explored. First, we assessed whether ApoA-I affects cellular energetics through analysis of mitochondrial metabolism with Seahorse Analyzer. As well as that, we employed a molecular biosensor of ATP:ADP ratio PercevalHR. Finally, we studied the exocytosis process in response to ApoA-I treatment. We confirmed that ApoA-I mediated cellular modulations in beta cells increase insulin secretion and propose that this is in one way achieved through enhanced cellular respiration. (Less)
- Popular Abstract
- What makes the “good cholesterol” so great?
Diabetes is an alarming health problem and one of the main causes of death in the world. Currently, there are 422 million diabetic patients with numbers rising every day. It is important that we research this disease and learn how to successfully prevent and treat it.
Generally, we divide diabetes into two groups. Type 1 is an autoimmune, genetic disorder that often appears in the childhood. On the other hand, type 2 usually develops later in life. Type 2 diabetes is the focus of this thesis so let’s explain its mechanism in more detail.
After eating, food is digested into glucose, a small sugar molecule. Glucose then circulates in the blood until it is taken up by the cells. This is... (More) - What makes the “good cholesterol” so great?
Diabetes is an alarming health problem and one of the main causes of death in the world. Currently, there are 422 million diabetic patients with numbers rising every day. It is important that we research this disease and learn how to successfully prevent and treat it.
Generally, we divide diabetes into two groups. Type 1 is an autoimmune, genetic disorder that often appears in the childhood. On the other hand, type 2 usually develops later in life. Type 2 diabetes is the focus of this thesis so let’s explain its mechanism in more detail.
After eating, food is digested into glucose, a small sugar molecule. Glucose then circulates in the blood until it is taken up by the cells. This is done with the help of a hormone called insulin. Our cells then use glucose to make energy. But with diabetic patients, this process doesn’t work as it should. Their bodies don’t make enough insulin and their cells don’t take up glucose. That means that their blood sugar remains chronically high, which can be very dangerous.
To treat diabetes, we are researching ways to increase insulin production and lower blood sugar levels. Two interesting molecules that can perhaps do both are HDL and its main protein part Apolipoprotein A-I or ApoA-I in short. HDL stands for high-density lipoprotein but it is more commonly known as the “good cholesterol”. It has gained this title because it can prevent atherosclerosis: a build-up of fats and cholesterol on walls of arteries that can cause heart attacks. Studies have shown that HDL and ApoA-I could be used for the treatment of diabetes because they can lower blood sugar levels. Not only that but our group also found that cells previously treated with ApoA-I secrete much more insulin.
In this thesis, I wanted to better understand the mechanism behind ApoA-I action and explain how ApoA-I boosts insulin levels. So, I looked into different steps of the molecular pathway that leads to insulin secretion. Specifically, I investigated if ApoA-I affects cellular energy production in mitochondria. For that, I used Seahorse Flux Analyzer and molecular ATP:ADP ratio biosensor PercevalHR. I also checked if ApoA-I influences insulin release from pancreatic cells with the Western blot method.
In this project, I confirmed that pancreatic cells treated with ApoA-I produce more insulin. I found that ApoA-I might increase mitochondrial respiration and energy production. This extra energy may then be used for enhanced insulin secretion. This thesis further confirms that ApoA-I is an interesting molecule with therapeutic potential.
Master’s Degree Project in Molecular Biology 45 credits 2021
Department of Biology, Lund University
Supervisors: Claire Lyons and Lena Eliasson
Medical Protein Science, Department of Experimental Medical Science, Faculty of Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9043918
- author
- Mohar, Manca
- supervisor
-
- Claire Lyons LU
- Lena Eliasson LU
- organization
- course
- MOBN02 20202
- year
- 2021
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9043918
- date added to LUP
- 2021-05-11 12:57:12
- date last changed
- 2021-05-11 12:57:12
@misc{9043918,
abstract = {{High density lipoprotein (HDL) and its principal protein component Apolipoprotein A-I (ApoA-I) are commonly recognised for their anti-cardiovascular disease properties. Multiple studies have indicated that they also have important roles in the context of glycaemic control and diabetes. Low levels of HDL and ApoA-I have been linked to increased risk of diabetes development. Furthermore, it has been shown that HDL and ApoA-I have the ability to reduce plasma glucose and increase insulin secretion. This beneficial effect on glucose metabolism gives them therapeutic potential. Our group previously showed that preincubation with ApoA-I enhances insulin secretion in a beta cell line. The main goal of this thesis was to explain the biological mechanism behind this process and different steps of glucose stimulated insulin secretion pathway were explored. First, we assessed whether ApoA-I affects cellular energetics through analysis of mitochondrial metabolism with Seahorse Analyzer. As well as that, we employed a molecular biosensor of ATP:ADP ratio PercevalHR. Finally, we studied the exocytosis process in response to ApoA-I treatment. We confirmed that ApoA-I mediated cellular modulations in beta cells increase insulin secretion and propose that this is in one way achieved through enhanced cellular respiration.}},
author = {{Mohar, Manca}},
language = {{eng}},
note = {{Student Paper}},
title = {{Role of Apolipoprotein A-I in the regulation of insulin secretion from pancreatic beta cells}},
year = {{2021}},
}