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Abstract
Type 1 diabetes (T1D) is a worldwide disease that affects about 1% population. Approximate 1.3 million Americans have T1D with 40,000 new cases each year. T1D is an autoimmune disease caused by T cell-mediated elimination of pancreatic β cells responsible for producing insulin, a peptide hormone that regulates the extracellular and intracellular balance of glucose in muscle, liver, and adipose tissue. Insulin functions through its receptor to up-regulate the level of glucose transporters on cell membrane facilitating glucose influx into cells as the source of energy. Lack of insulin in T1D patients leads to too much of glucose in the blood (hyperglycemia) and not sufficient glucose in the cells, resulting in polyphagia, glycosuria, polyuria, polydipsia and other pathological conditions which, with time, lead to blindness, numbness, ulcer/amputation, heart diseases, and eventual death. The most effective treatment option currently available for T1D is insulin therapy. In average, 3 - 4 daily insulin injections are required for T1D patients. Such a treatment, while common and effective, is not without risk. Timely injection of a proper amount of insulin is hard to achieve in patients as blood glucose level fluctuates depending on the type and amount of food a patient takes, physical activities and other physiological conditions. Insulin overdose happens and could lead to hypoglycemia, loss of consciousness and seizure among other detrimental effects. Significant efforts have been made in
the past to optimize insulin administration. At the same time, research has been conducted to develop a safer and more effective alternative. Among many approaches taken, cell reprogramming to convert non-insulin producing cells into β or β-like cells has attracted most attention. The cell-reprogramming approach aims at replacing the missing β cells in T1D with new insulin-producing cells to regain the control of glucose metabolism. The goal of this thesis is to provide an overview and recent progress made in the use of cell reprogramming as a potential new treatment for T1D. Being relatively new research area, the studies summarized here are mostly preclinical but limited clinical progresses are also discussed.
the past to optimize insulin administration. At the same time, research has been conducted to develop a safer and more effective alternative. Among many approaches taken, cell reprogramming to convert non-insulin producing cells into β or β-like cells has attracted most attention. The cell-reprogramming approach aims at replacing the missing β cells in T1D with new insulin-producing cells to regain the control of glucose metabolism. The goal of this thesis is to provide an overview and recent progress made in the use of cell reprogramming as a potential new treatment for T1D. Being relatively new research area, the studies summarized here are mostly preclinical but limited clinical progresses are also discussed.