The role of b-cell keratins in islet histology, glucose uptake, and diabetes susceptibility
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Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
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DOI
Tiivistelmä
β-cells along with several types of other cells compose the endocrine pancreas
and they produce the hormone insulin which has a role in the regulation of glucose in the
bloodstream. A disruption in insulin production and its secretion in β-cells causes
diabetes. Keratins (K) are members of the intermediate filament protein family and they
are known for both mechanical and physiological activity in cells. Their role is
emphasized by 80 human diseases caused by keratin filament mutations. The most
common types of keratins in the endocrine pancreas are K8 and K18 and the global K8
knockout in mice leads to the mislocalization of glucose transporter 2 (GLUT2). Three
aims were set for this thesis: evaluate the connection between keratins and proliferation
in β-cells, study the role of keratins in β-cells during streptozotocin-induced diabetic
stress, and understand the role of keratins in β-cells during glucose uptake. Histology
analysis showed that bigger islets are present in β-cell-specific K8 knockout mice
compared to the wild type. The analysis of β-cell proliferation-related parameters showed
no difference in these mice compared to the control. Digital and quantitative histological
analysis of the samples from short-term streptozotocin-treated mice showed the K8
conditional knockout mice have lower islet damage compared to the control and were
thus, less susceptible to this diabetic model. No differences were seen in islet size, islet
mass, and islet number in streptozotocin-treated mice compared to control. GLUT2
localization analysis showed that in β-cell-specific K8 knockout mice GLUT2 gets
mislocalized from the membrane to the cytoplasm compared to the control mice. The
assessment of the damage score and GLUT2 localization analysis showed that keratins
might have a role in the targeting of β-cell GLUT2 since streptozotocin is transported into
beta cells through GLUT2.