Graduation Year

2024

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Biology (Cell Biology, Microbiology, Molecular Biology)

Major Professor

Brant Burkhardt, Ph.D.

Committee Member

Mark Atkinson, Ph.D.

Committee Member

Stanley Stevens, Ph.D.

Committee Member

Meera Nanjundan, Ph.D.

Keywords

ethnopharmacology, Keap1/Nrf 2, Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is an autoimmune disorder that results in the destruction of the insulin producing pancreatic β cells. The only therapeutic option following T1D clinical onset is exogenous insulin supplementation. At present, there is no cure for T1D and attempted interventional therapy has been focused on modulating the immune system. Few attempts have been pursued at preserving β cell function and survival. Here we provide a novel approach using extract from the fruit of the Cornus officinalis (CO) tree to preserve β cell function through the prevention of β cell stress. CO has been used in traditional Chinese medicine to treat several aliments with contemporary research demonstrating CO has a therapeutic effect in type 2 diabetes. My in vitro findings using a human pancreatic cell line demonstrate that CO induces a robust activation of the critical Keap1/Nrf2 antioxidant pathway and inhibit hydrogen peroxide induced cell death. To further extrapolate these findings, we then performed an in vivo analysis in which we treated the non-obese diabetic mouse (NOD) with an oral gavage of CO. We found that CO significantly delayed T1D onset, hyperglycemia, pancreatic insulitis and preserved c-peptide secretion indicating a preservation of β cell mass and function. Individual composition analysis was performed using HPLC and mass spectrometry to reveal specific fractions within CO are inducing the biological effects. Taken together, our study has demonstrated the therapeutic potential and mechanism of action for CO as an interventional therapy of T1D.

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