Maf transcription factors in beta cell function
Författare
Summary, in Swedish
According to the International Diabetes Federation (IDF), 415 million people suffer
from diabetes worldwide. Diabetes occurs when the pancreatic beta cells are no longer
able to produce or properly use insulin. Insulin regulates blood glucose levels by
enabling glucose uptake into cells, providing the body with energy. Elevated glucose
levels cause damages to highly vascularized organs such as heart, kidney and eyes.
Other complications include nerve damage and metabolic difficulties. There is
currently no cure for diabetes and diabetic individuals depend on regular insulin
injections to control blood glucose levels. In order to treat and finally cure diabetes, it
is important to understand the underlying causes of the disease and broaden our
understanding of the complex function of the insulin producing beta cells. Our
research focuses on the development and function these cells. In addition to glucose,
insulin release can be controlled through communication between beta cells and the
central nervous system (CNS). This communication is critical for both acute and long
term blood glucose control. However, very little is known about how beta cells
communicate with the nervous system. Combining genetic and physiological studies
in cells, mice and to some extent human subjects, I have investigated how different
factors affect glucose metabolism and what happens when these factors are impaired
or removed. My results have shown that a specific protein, MafA, is crucial for the
CNS-beta cell interaction. MafA can regulate this process by directly controlling
distinct genes. Genes regulated by MafA are essential for neurotransmitter-mediated
regulation of blood glucose levels. These genes include nicotinic acetylcholine
receptors, proteins essential for neurotransmitter signaling, and monoamine oxidases
(A and B), proteins that metabolize specific neurotransmitters and thereby maintain a
balance of the signals regulating blood glucose levels. Additionally, my results show
that MafA controls the expression of genes involved in different aspects of beta cell
function, ranging from the level of neurotransmitters and their receptors to the
expression, release and storage of insulin. Furthermore, our studies on adult beta cells
identified a novel protein important for blood glucose control, Mitf. Deletion of the
Mitf gene in mice resulted in increased insulin release and faster blood glucose
clearance. Researchers have found links between long term increases in blood glucose
levels and depression, a condition originating in the brain. Understanding how the
brain and the pancreas communicate in order to influence the production and release
of insulin and thus maintain normal glucose control could open up new possibilities
in improving the function of beta cells and treating diabetes.
Avdelning/ar
Publiceringsår
2015
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University Faculty of Medicine Doctoral Dissertation Series
Volym
2016:10
Fulltext
- Available as PDF - 10 MB
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Dokumenttyp
Doktorsavhandling
Förlag
Stem Cell Center, Lund University
Ämne
- Cell and Molecular Biology
Nyckelord
- Beta cell
- MafA
- type 2 diabetes
- insulin secretion
- transcription
- monoamine oxidase
- MaoA
- MaoB
- nicotinic receptor subunits
- nAChRs
Status
Published
Handledare
- Isabella Artner
- Henrik Semb
- Edgar Pera
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-7619-235-1
Försvarsdatum
25 januari 2016
Försvarstid
09:30
Försvarsplats
Segerfalkssalen, Wallenberg Neurocentrum, BMC A10, Lund University
Opponent
- Palle Serup (Professor)