Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

Examining the Co-localization and Distribution of Insulin Receptor on CD3 Cells in Type 1 Diabetic Human Pancreatic Cadaver Samples

Al Huniti, Tasneem
http://rave.ohiolink.edu/etdc/view?acc_num=mco1596621272423573

Abstract Details

2020, Master of Science (MS), University of Toledo, Medicinal Chemistry.
Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease characterized by destruction of pancreatic β-cells, which leads to hyperglycemia and development of ketoacidosis. Patients with T1D constitute 5-10% of all people in the diabetes population worldwide. (1). T1D usually presents in childhood or adolescence; nevertheless, the disease can appear at any time of life. (2) The knowledge of the pathogenesis and the development of type 1 diabetes has been enhanced in the last decade. High risk pre-diabetic individuals can be detected by the presence of characteristic autoantibodies and by genetic biomarkers. T1D is a heterogeneous disease where there is a delicate interplay between genes, autoantibodies, and environmental effects. A hallmark feature of T1D is “insulitis”, which is a multifocal inflammatory reaction characterized by relatively subtle leucocytic infiltration, in which CD8+ T cells mediate cytotoxicity being directed towards insulin producing islets in the pancreas (3). A lesser explored role of the insulin receptor (IR) is the chemotactic function, which helps the cells to physically move towards a concentrated source of insulin. Our lab focused on the chemotactic role of the over expressed IR on the infiltrated T cells that attack the insulin producing beta cells in the pancreas. A novel transgenic animal model with insulitis that results from increased insulin receptor expression on T cells in a non-diabetic C57BL/6 background has been engineered. In this model the animals have diminished glucose tolerance in response to an intraperitoneal injection of glucose, but do not become diabetic. (4) The overall hypothesis is that insulin receptor expression on T cells allows for chemotaxis to the islets causing insulitis. In the past, our lab examines this theory on age matched C57BL/6 as a control and on the novel engineered transgenic mice (non- diabatic C57BL/6 with high IR expression on T -cells). Preliminary data shows that C57Bl/6 transgenic mice with 3xFLAG tagged mIR engineered behind the CD3 promoter and enhancer elicited T cell insulitis in this normal mouse strain. This suggests that a high density of IR expression on T cells may be engaged in T cell migration into the pancreas. Now, we are moving forward to test this hypothesis on normal and diabetic human samples. By utilizing an immunofluorescence technique to visualize the colocalization of the IR and CD3 biomarkers on the infiltrated T- cells that attack the human beta cells.
Marcia McInerney (Committee Chair)
Shah Zahoor (Committee Member)
Katherine Wall (Committee Member)
Pharmacy Sciences

Recommended Citations

Citations

  • Al Huniti, T. (2020). Examining the Co-localization and Distribution of Insulin Receptor on CD3 Cells in Type 1 Diabetic Human Pancreatic Cadaver Samples [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1596621272423573

    APA Style (7th edition)

  • Al Huniti, Tasneem. Examining the Co-localization and Distribution of Insulin Receptor on CD3 Cells in Type 1 Diabetic Human Pancreatic Cadaver Samples . 2020. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1596621272423573.

    MLA Style (8th edition)

  • Al Huniti, Tasneem. "Examining the Co-localization and Distribution of Insulin Receptor on CD3 Cells in Type 1 Diabetic Human Pancreatic Cadaver Samples ." Master's thesis, University of Toledo, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=mco1596621272423573

    Chicago Manual of Style (17th edition)

mco1596621272423573
73
© 2020, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.