Initial Characterization of a Multifaceted Small Molecule and Its Efficacy for the Treatment of Type 1 Diabetes Mellitus
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| Language: | English |
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Ohio University / OhioLINK
2021
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1617098329334351 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-ohiou16170983293343512021-08-03T07:16:59Z Initial Characterization of a Multifaceted Small Molecule and Its Efficacy for the Treatment of Type 1 Diabetes Mellitus Koch, William J. Biomedical Research Medicine Physiology Immunology Biochemistry pancreas islets of Langerhans beta-cells type 1 diabetes mellitus drug discovery Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which insulin-secreting beta cells found within the pancreatic islets of Langerhans are destroyed by the immune system, thereby resulting in unregulated high blood sugar. Although much has been discovered regarding the numerous risk factors and the pathogenesis of this disease, current therapies for T1DM merely address the tip of the iceberg. With the identification of “pancreatic diabetes” in 1889 and the discovery of insulin in 1921, these revolutionary accomplishments have fallen short in eradicating T1DM. As no cure exists, individuals with T1DM are dependent on insulin replacement to survive. Therefore, in the 21st century, it is time to reevaluate the way in which T1DM is treated as new strides move towards a more preventative approach. For decades, it has been understood that beta-cell death, associated with T1DM, involves a complex signaling cascade initiated by cytokines (IL-1Β, TNF-α and IFN-γ). Both IL-1Β and TNF-α induce NF-κB expression, while IFN-γ induces JAK/STAT expression, thereby collectively leading to the destruction of beta-cell function and mass. Here we have identified a small molecule that suppresses cytokine-induced and endoplasmic reticulum (ER) stress-induced beta-cell destruction, as well as promotes insulin production and secretion. After screening nearly 50 compounds, we identified a potent lead compound. These efforts led to the initial classification of a prospective target for the dual effects of our compound. Lastly, using a type 1 diabetic mouse model (NOD mice), we observed the in vivo effects of our compound whereby hyperglycemia is lowered, and insulitis is reduced. 2021-06-01 English text Ohio University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1617098329334351 http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1617098329334351 restricted--full text unavailable until 2026-05-01 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biomedical Research Medicine Physiology Immunology Biochemistry pancreas islets of Langerhans beta-cells type 1 diabetes mellitus drug discovery |
| spellingShingle |
Biomedical Research Medicine Physiology Immunology Biochemistry pancreas islets of Langerhans beta-cells type 1 diabetes mellitus drug discovery Koch, William J. Initial Characterization of a Multifaceted Small Molecule and Its Efficacy for the Treatment of Type 1 Diabetes Mellitus |
| author |
Koch, William J. |
| author_facet |
Koch, William J. |
| author_sort |
Koch, William J. |
| title |
Initial Characterization of a Multifaceted Small Molecule and Its Efficacy for the Treatment of Type 1 Diabetes Mellitus |
| title_short |
Initial Characterization of a Multifaceted Small Molecule and Its Efficacy for the Treatment of Type 1 Diabetes Mellitus |
| title_full |
Initial Characterization of a Multifaceted Small Molecule and Its Efficacy for the Treatment of Type 1 Diabetes Mellitus |
| title_fullStr |
Initial Characterization of a Multifaceted Small Molecule and Its Efficacy for the Treatment of Type 1 Diabetes Mellitus |
| title_full_unstemmed |
Initial Characterization of a Multifaceted Small Molecule and Its Efficacy for the Treatment of Type 1 Diabetes Mellitus |
| title_sort |
initial characterization of a multifaceted small molecule and its efficacy for the treatment of type 1 diabetes mellitus |
| publisher |
Ohio University / OhioLINK |
| publishDate |
2021 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1617098329334351 |
| work_keys_str_mv |
AT kochwilliamj initialcharacterizationofamultifacetedsmallmoleculeanditsefficacyforthetreatmentoftype1diabetesmellitus |
| _version_ |
1719458088514224128 |