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Regulation Of Glucose Homeostasis By The Phlpp1 Phosphatase, Kara L. Larson

Theses and Dissertations--Molecular and Cellular Biochemistry

Type 2 diabetes mellitus is a metabolic disease that affects one in ten people in the United States. It is caused by a combination of genetics and lifestyle factors. Disease progression begins with insulin resistance in peripheral tissues followed by pancreatic beta-cell failure. The mechanisms behind disease progression are not completely understood. PH domain leucine rich repeat protein phosphatase 1 (PHLPP1) is a known regulator of Akt and other members of the AGC kinase family. Akt has been established to play a role in numerous metabolic signaling pathways, including insulin action. It is hypothesized that as a regulator of Akt, …

The Role Of Scavenger Receptor Class B Type I-Regulated Inducible Glucocorticoids In Sepsis, Junting Ai

Theses and Dissertations--Nutritional Sciences

Sepsis claims over 215,000 lives in the US annually. Inducible glucocorticoids (iGC) is produced during sepsis. However, the precise effects of iGC in sepsis remain unclear due to a lack of appropriate animal models. Glucocorticoid (GC) insufficiency is associated with a marked increase in mortality and occurs in 60% of severe septic patients. Yet the conclusion of GC therapy on septic patients is still controversial.

Scavenger receptor class B type I (SR-BI) in the adrenal mediates the selective uptake of cholesteryl ester from lipoproteins for GC synthesis. SR-BI-/- mice completely lack iGC during sepsis and are highly susceptible to septic …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …