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Full-Text Articles in Cell Biology

Unraveling The Beta Cell Translatome: Elucidation Of An Erk/Hnrnpk/Jund Axis, Austin Lewis Good Jan 2019

Unraveling The Beta Cell Translatome: Elucidation Of An Erk/Hnrnpk/Jund Axis, Austin Lewis Good

Publicly Accessible Penn Dissertations

In type 2 diabetes, oxidative stress contributes to the dysfunction and loss of pancreatic β cells. A highly conserved feature of the cellular response to stress is the regulation of mRNA translation, however, the mechanisms underlying this process in β cells are not fully understood. Here we use TRAP-seq to examine changes in the ribosome occupancy of mRNAs during conditions associated with β cell dysfunction, leading us to identify a cohort of translationally regulated genes with 3’UTR enrichment of a cytosine-rich motif. Of particular interest was the gene encoding JUND, a transcription factor with anti-oxidant functions in other cell ...


Epigenetic Regulation Of The Dlk1-Meg3 Imprinted Locus In Human Islets, Vasumathi Kameswaran Jan 2016

Epigenetic Regulation Of The Dlk1-Meg3 Imprinted Locus In Human Islets, Vasumathi Kameswaran

Publicly Accessible Penn Dissertations

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by inadequate insulin secretion by the pancreatic β-cell in response to increased blood glucose levels. Despite compelling evidence that T2DM has a high rate of familial aggregation, known genetic risk variants account for less than 10% of the observed heritability. Consequently, post-transcriptional regulators of gene expression, including microRNAs and other noncoding RNAs, have been implicated in the etiology of T2DM, in part due to their ability to simultaneously regulate the expression of hundreds of targets.

To determine if microRNAs are involved in the pathogenesis of human T2DM, I sequenced ...


A Study Of The Role Of Gata6 In Definitive Endoderm Specification And Β-Cell Functionality By Genome Engineering Of Pluripotent Stem Cells, Amita Tiyaboonchai Jan 2016

A Study Of The Role Of Gata6 In Definitive Endoderm Specification And Β-Cell Functionality By Genome Engineering Of Pluripotent Stem Cells, Amita Tiyaboonchai

Publicly Accessible Penn Dissertations

Human pluripotent stem cells (PSCs) provide a powerful model system for the study of early human development, disease modeling and physiology. We chose to focus our studies on monogenic diabetes using this model system. Within the pancreas, β cells are one of the most critical endocrine cells as loss of this cell type disrupts blood glucose homeostasis, leading to diabetes. Due to the limited availability of primary human cells it is difficult to study them in vitro, especially in the context of genetic disease where patient material is even more difficult to obtain. Here, we characterize endodermal progenitor (EP) derived ...


Akt Controls Adipocyte Function And Systemic Metabolism, Abigail Shearin Jan 2016

Akt Controls Adipocyte Function And Systemic Metabolism, Abigail Shearin

Publicly Accessible Penn Dissertations

ABSTRACT

AKT CONTROLS ADIPOCYTE FUNCTION AND SYSTEMIC METABOLISM

Abigail L. Shearin

Morris J. Birnbaum

Adipose tissue is a key regulator of energy homeostasis. Diseases with an increase or decrease in adiposity result in perturbations of systemic metabolism. The insulin signaling and insulin-like growth factor 1 (IGF-1) cascades are vital to the function of many tissues during development and in the mature organism. AKT, a Ser/Thr kinase, is a central node in the insulin and IGF-1 pathways. In the liver, much is known about the consequences when insulin-AKT signaling is lost, but adipose tissue has presented a unique challenge to ...


Regulators Of Mouse And Human Beta Cell Proliferation, Yang Jiao Jan 2013

Regulators Of Mouse And Human Beta Cell Proliferation, Yang Jiao

Publicly Accessible Penn Dissertations

Diabetes mellitus is an increasingly prevalent metabolic disorder that is estimated to affect over 300 million people by 2025. Common to either type 1 or type 2 diabetes is a progressive inadequacy of functional beta-cell mass. Recent studies have shown that during times of prolonged metabolic demand for insulin, the endocrine pancreas can respond by increasing beta-cell mass by beta-cell proliferation. Advances that further our knowledge of the molecular factors that control beta-cell proliferation will be crucial for understanding the homeostasis of beta-cell mass during adulthood, and are pivotal for any attempt to use instructive cues to induce the proliferation ...