Date of Award

5-2021

Culminating Project Type

Thesis

Degree Name

Biological Sciences - Cell and Molecular: M.S.

Department

Biology

College

College of Science and Engineering

First Advisor

Dr. Marina Cetkovic-Cvrlje

Second Advisor

Dr. Oladele Gazal

Third Advisor

Dr. Bruce Jacobson

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Keywords and Subject Headings

Type 1 Diabetes (T1D), Mouse streptozotocin model of T1D, Sodium Bicarbonate, Autoimmune Disease, T cells

Abstract

Type one diabetes (T1D) is an inflammatory autoimmune disease in which T cells coordinate and carry out an attack on insulin-producing beta cells in the pancreas. Currently, the only treatment for T1D is life-long insulin injections, which cause great financial burden for T1D patients and their families. Thus, it is crucial to explore cheaper preventative and treatment options. Previous studies have shown that sodium bicarbonate (SB), an alkalinizing agent that is typically used to treat indigestion, has the potential to reduce inflammation through its action on macrophages. Thus, it was hypothesized that SB administration would decrease the incidence and severity of T1D by its action on T cells in two mouse models, chemically (streptozotocin; STZ)-induced T1D in C57BL/6J mice (STZ-B6 model) and spontaneously-developing T1D in NOD/LtJ (NOD) mice. Seven-week-old B6 and nine-week-old NOD mice were administered low-dose SB (20 mM) or high-dose SB (200 mM) via drinking water until the experimental endpoints when B6 mice were 12-weeks-old and NOD mice were 12-weeks or 24-weeks-old. At eight weeks of age, T1D was induced by STZ injections in B6 mice. Blood glucose and body weight measurements were taken biweekly, in STZ-B6 groups, and weekly, in NOD groups for the same duration as SB treatment administration. At experimental endpoints, mice were euthanized, and the effects of SB on T cells were observed, by investigating the T cell proliferation (splenocytes culture with an addition of a T cell mitogen), T cell immunophenotypes (flow cytometry), and pro-inflammatory and anti-inflammatory cytokines (flow cytometry). High dose SB significantly decreased T1D incidence in STZ-B6 mice and glycemia levels in NOD mice at the early timepoint. A low-dose SB treatment, while exhibiting trends, did not significantly decrease the development and glycemia levels in both murine T1D models. Both high- and low-dose SB did not have prominent effects on T cell proliferation, composition, or cytokines, besides the trends in lowering proliferation and proinflammatory cytokines at the experimental endpoints. Overall, our results, while promising, do not support SB as a major player in preventative efforts in the fight against T1D, highlighting the need for further research in this area.

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