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Effects Of High Glucose On Autophagy And Apoptosis In Preimplantation Mouse Embryo Culture, Virginia Wolfe Jun 2023

Effects Of High Glucose On Autophagy And Apoptosis In Preimplantation Mouse Embryo Culture, Virginia Wolfe

Electronic Thesis and Dissertation Repository

Maternal diabetes increases congenital malformations due to teratogenic effects of glucose on the developing embryo. High glucose culture alters preimplantation embryo development and is associated with increased oxidative stress. Apoptosis and autophagy are programmed cell death and survival mechanisms induced by oxidative stress, but their role in preimplantation diabetic embryopathy is poorly elucidated. It was hypothesized that high glucose culture would alter autophagic and apoptotic responses, and that they are dependent on the timing of high glucose culture initiation. Embryos were cultured with 0.2 mM (control) or 25 mM (high glucose) of D-glucose starting from the early (36 hpi) or …


Characterization Of The Principal And Secondary Islets During Pancreatic Development In Zebrafish With A Crispr-Mediated Glis3 Knockout, Caleb Harsin Apr 2023

Characterization Of The Principal And Secondary Islets During Pancreatic Development In Zebrafish With A Crispr-Mediated Glis3 Knockout, Caleb Harsin

Honors College Theses

The Krüppel-like transcription factor, Gli-similar 3 (Glis3) has been implicated in several human pathologies including neonatal diabetes, congenital hypothyroidism, and polycystic kidney disease. Numerous genome-wide association studies (GWAS) have additionally identified Glis3 as a risk locus for the development of both type 1 and type 2 diabetes mellitus. Our previous data suggest possible roles for Glis3 in endocrine pancreas specification in mice, but despite its clinical significance, much remains unknown about the role(s) Glis3 plays during development. To elucidate Glis3 gene function, a CRISPR-mediated knockout line of zebrafish was developed by deleting a segment of the Glis3 coding region …


Tgif1 Physiological Levels Limit Β-Cell Distress And Neonatal Diabetes, Creighton J. Friend Jan 2023

Tgif1 Physiological Levels Limit Β-Cell Distress And Neonatal Diabetes, Creighton J. Friend

Theses and Dissertations

TGIF1 belongs to the superfamily of homeodomain proteins, which regulate a wide variety of biological functions, including cell stemness and specification of cell fate during early development. Perhaps surprisingly, we found that enforced expression in pancreatic progenitor cells during embryogenesis resulted in severe diabetes, hinting at the possibility that TGIF1 might regulate pancreas development. Subsequent genetic experiments targeting β-cells showed that TGIF1 affected β-cell function and homeostasis. Transcriptomic analysis revealed that TGIF1 expression inhibits the expression of essential components of UPR signaling, underscoring a potential mechanism in which TGIF1 disrupts protein folding and secretion. Congruently, TGIF1 expression led to a …