- Title
- The effect of ER stress in INS-1E cells using IL-1β under hyperglycaemic conditions
- Creator
- Jackson, Simon
- Subject
- Diabetes -- Pathogenesis
- Subject
- Endoplasmic reticulum -- Pathophysiology Endoplasmic reticulum Diabetes
- Date Issued
- 2018
- Date
- 2018
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- http://hdl.handle.net/10948/30397
- Identifier
- vital:30938
- Description
- Diabetes afflicts millions of individuals worldwide, and the statistics rise each year. It is associated with various ailments which reduce the quality of life and has been shown to be associated with seemingly unrelated diseases or conditions. One aspect of the pathogenesis of diabetes is endoplasmic reticulum (ER) stress, which is an imbalance in the protein loading and protein folding capacities of the ER of a cell. Under chronic hyperglycaemic conditions associated with the development of diabetes, excessive insulin production disrupts the ER homeostasis, leading to ER stress. If the ER stress is severe or chronic, cell death of pancreatic β-cells may occur, leading to the onset of diabetes. There is currently a gap in available models that closely resemble the pathogenesis of diabetes in insulinoma-1E (INS-1E) pancreatic β-cells to study ER stress under hyperglycaemic conditions. This study optimised various ER stress-inducing models and tested terpenoid treatments to investigate their potential in modulating ER stress. Using various cell viability assays, five models to induce ER stress were optimised (hyperglycaemic, interleukin-1β (IL-1β), tunicamycin (Tm), brefeldin-A (BFA) and thapsigargin (Tg)). The five models were shown to induce ER stress through the expression of the downstream ER stress marker CCAAT-enhancer binding protein (C/EBP) homologous protein (CHOP). The various models induced ER stress under different mechanisms. Insulin secretion analysis using enzyme-linked immunosorbent assays (ELISAs) demonstrated that low concentrations of IL-1β promoted insulin secretion. Several of the terpenoid treatments showed potential in alleviating different aspects of either ER stress or inflammation.
- Format
- xviii, 173 leaves
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
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Thumbnail | File | Description | Size | Format | |||
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View Details Download | SOURCE1 | Simon Jackson.pdf | 4 MB | Adobe Acrobat PDF | View Details Download |