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Full text release has been delayed at the author's request until May 13, 2028

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Characterizing the Effects of Novel Compounds on Pancreatic Islets for Type 1 Diabetes

Bogart, Maislin C
http://orcid.org/0000-0001-7701-3246
http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1682524052655173

Abstract Details

2023, Bachelor of Science (BS), Ohio University, Biological Sciences.
Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the loss of the only insulin secreting cells in the human body, the pancreatic beta-cells. Exogenous insulin is used to control the resulting hyperglycemia and replace the lack of insulin, but it is not a cure. To cure T1D, the autoimmune destruction of beta-cells must cease, and insulin secretory capacity must be restored. We have identified a novel compound that both protects against cytokine-induced cell death and stimulates insulin secretion from mouse islets. Importantly, I demonstrate that this compound exhibits protection from overnight cytokine treatment and enhances insulin secretion from human islets. Surprisingly, acute exposure to this compound severely reduced intracellular calcium. These findings conflict with observed effects on insulin secretion. However, the onset of enhanced insulin secretion appears between 2 and 4 hours with a maximal effect around 12 hours. In addition, the insulin secretory effects are shown to remain and enhance the response to glucose stimulation even after washout as treated islets showed increased insulin secretion in high glucose compared to control and glipizide-treated islets. We also found that our compound was one out of two compounds tested that augmented overnight insulin secretion. Testing of the amplifying pathway of insulin secretion revealed that this compound does enhance insulin secretion through this pathway. Finally, our lead experimental compound shows varying protection against ER stressors thapsigargin, brefeldin A, and tunicamycin. Overall, these findings suggest the small-molecule compounds we are developing and testing may hold therapeutic potential for treating type 1 diabetes through their dual action.
Craig S Nunemaker (Advisor)
94 p.
Biology; Biomedical Research; Cellular Biology
type 1 diabetes mellitus; islets; beta-cells; therapeutics; cytokines; inflammation; insulin secretion; intracellular calcium; ER stress

Recommended Citations

Citations

  • Bogart, M. C. (2023). Characterizing the Effects of Novel Compounds on Pancreatic Islets for Type 1 Diabetes [Undergraduate thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1682524052655173

    APA Style (7th edition)

  • Bogart, Maislin. Characterizing the Effects of Novel Compounds on Pancreatic Islets for Type 1 Diabetes. 2023. Ohio University, Undergraduate thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1682524052655173.

    MLA Style (8th edition)

  • Bogart, Maislin. "Characterizing the Effects of Novel Compounds on Pancreatic Islets for Type 1 Diabetes." Undergraduate thesis, Ohio University, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1682524052655173

    Chicago Manual of Style (17th edition)

ouhonors1682524052655173
© 2023, all rights reserved.
This open access ETD is published by Ohio University Honors Tutorial College and OhioLINK.