Pharmacology Commons^™

Small Gtp-Binding Proteins In Insulin Secretion, Bhavaani Jayaram

Wayne State University Dissertations

Type 2 diabetes mellitus is marked by a substantial beta-cell failure which is characterized by defective insulin secretion and resistance to insulin. Understanding the molecular events leading to Glucose-stimulated insulin secretion [GSIS] might serve as therapeutic potential towards diabetes. GSIS involves interplay between small G-proteins and their regulatory factors. Herein, I tested the hypothesis that Arf nucleotide binding site opener [ARNO], a guanine nucleotide exchange factor [GEF] for the small G-protein Arf6, mediates the activation of Arf6, and that ARNO/Arf6 signaling axis, in turn, controls the activation of downstream effectors. Salient features of my study are: [i] ARNO/Arf6 is expressed …

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …

Compensatory Renal Hypertrophy, Mitochondria And Redox Status, Bavneet Benipal

Wayne State University Dissertations

A reduction in functional renal mass occurs in humans during aging and severe kidney damage from diseases, injuries, infections and congenital conditions and after nephrectomy. Nephrectomy, or surgical removal of a kidney or a section of a kidney, is performed for treatment of unilateral secondary renal cancer, infections and for kidney transplantation. As a result, the remaining renal tissue undergoes compensatory growth due primarily to hypertrophy, in which both the size and functional capacity of the remaining kidney are increased. Renal compensatory hypertrophy is associated with a series of physiological, morphological and biochemical changes that also have toxicological implications.

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Mechanisms Of Regulation Of Islet Function By Nadph Oxidase, Ismail Syed

Wayne State University Dissertations

Glucose stimulated insulin secretion (GSIS) involves a series of metabolic and cationic events, leading to translocation of insulin-laden secretory granules from a distal site toward the plasma membrane for fusion and release of insulin into circulation. Vesicular transport and fusion events are tightly regulated by signals which coordinate between vesicle- and membrane-associated docking proteins. It is now being accepted that reactive oxygen species [ROS] plays a second messenger role in islet â-cell function. Further, evidence from multiple laboratories suggests a tonic increase in ROS generation is necessary for GSIS and fatty acid-induced insulin secretion. On the other hand, excessive ROS …