Quantitative Analysis of Paracrine Interactions of α- and β-Cells In Pancreatic Islets
Brown, Aedan R.
2023
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Diabetes occurs when blood sugar levels are improperly regulated due to an inability to secrete insulin. Therapies that stimulate or restore insulin secretion help alleviate the symptoms diabetic patients experience. Insulin is secreted from β-cells in the pancreatic islets of Langerhans, which also contain α-cells that secrete glucagon. Glucagon can stimulate insulin secretion, so improving the ... read moreunderstanding of α-cells and glucagon in the islets could provide new opportunities for diabetes therapeutics. Glucose is known to influence glucagon secretion, but experiments measuring glucagon secretion in response to glucose in vitro disagree as to the manner of this control. Isolated α-cells indicated glucose stimulates glucagon secretion in a Hill-like fashion, while experiments with pancreatic islets suggest a ‘U’-shaped response. I worked to reconcile this by developing a mathematical model of α- and β-cells in the pancreatic islets. This model captures both the transient secretion responses, as well as the paracrine relationships between the different hormones. Simulations using this model indicated that glucose may truly simulate glucagon secretion, but insulin’s inhibitory action helps to create the U-shape observed in islets. This trend helps to explain the hyperglucagonemia seen in type 1 diabetes and highlights the importance of experimental conditions for future work. Additionally, this work can contribute to future models, such as those simulating organs in vivo or lab-on-a-chip devices in vitro.Advisor: Professor Emmanuel Tzanakakis
Thesis (B.S.C.H.E.)--Tufts University, 2021.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: Emmanuel Tzanakakis.read less - ID:
- xg94j4726
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