Kinetics of Rab27a-dependent actions on vesicle docking and priming in pancreatic Β-cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65888/1/jphysiol.2008.158477.pd

Essential Role of the Small GTPase Ran in Postnatal Pancreatic Islet Development

The small GTPase Ran orchestrates pleiotropic cellular responses of nucleo-cytoplasmic shuttling, mitosis and subcellular trafficking, but whether deregulation of these pathways contributes to disease pathogenesis has remained elusive. Here, we generated transgenic mice expressing wild type (WT) Ran, loss-of-function Ran T24N mutant or constitutively active Ran G19V mutant in pancreatic islet β cells under the control of the rat insulin promoter. Embryonic pancreas and islet development, including emergence of insulin+ β cells, was indistinguishable in control or transgenic mice. However, by one month after birth, transgenic mice expressing any of the three Ran variants exhibited overt diabetes, with hyperglycemia, reduced insulin production, and nearly complete loss of islet number and islet mass, in vivo. Deregulated Ran signaling in transgenic mice, adenoviral over-expression of WT or mutant Ran in isolated islets, or short hairpin RNA (shRNA) silencing of endogenous Ran in model insulinoma INS-1 cells, all resulted in decreased expression of the pancreatic and duodenal homeobox transcription factor, PDX-1, and reduced β cell proliferation, in vivo. These data demonstrate that a finely-tuned balance of Ran GTPase signaling is essential for postnatal pancreatic islet development and glucose homeostasis, in vivo

Intracellular Serotonin Modulates Insulin Secretion from Pancreatic β-Cells by Protein Serotonylation

Non-neuronal, peripheral serotonin deficiency causes diabetes mellitus and identifies an intracellular role for serotonin in the regulation of insulin secretion

Gene Expression Profiling of a Mouse Model of Pancreatic Islet Dysmorphogenesis

In the past decade, several transcription factors critical for pancreas organogenesis have been identified. Despite this success, many of the factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor Hnf6 specifically in the pancreatic endocrine cell lineage resulted in disruptions in islet morphogenesis, including dysfunctional endocrine cell sorting, increased individual islet size, increased number of peripheral endocrine cell types, and failure of islets to migrate away from the ductal epithelium. The mechanisms whereby maintained Hnf6 causes defects in islet morphogenesis have yet to be elucidated.We exploited the dysmorphic islets in Hnf6 transgenic animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal total pancreas tissue from wild type and Hnf6 transgenic animals. Here we report the identification of genes with an altered expression in Hnf6 transgenic animals and highlight factors with potential importance in islet morphogenesis. Importantly, gene products involved in cell adhesion, cell migration, ECM remodeling and proliferation were found to be altered in Hnf6 transgenic pancreata, revealing specific candidates that can now be analyzed directly for their role in these processes during islet development.This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature beta cell function

A Comparative Study of the Usefulness of Accounting Systems

100 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2001.The main purpose of this study is to test whether the U.S. accounting system is more useful than other accounting systems in estimating firms' value by using a new method of comparing alternative accounting systems. This method examines whether one accounting system is superior to another accounting system with its ability to correctly measure a firm's worth, represented by the prevailing market price of its stock. Specifically, the analysis employs accounting-based valuation models developed by Ohlson (1995) and extended by Penman (1997). Two sets of sample are used in this study. The first sample consists of non-U.S. firms that report in Form 20F. These firms usually provide two different financial statements, one by their 'home' Generally Accepted Accounting Principles (GAAP) and the other by U.S. GAAP. The second sample consists of Japanese firms that are listed on at least one of the stock exchanges in Japan and that prepare consolidated financial statements on Japanese GAAP. For this sample, attempts are made to translate Japanese-GAAP based numbers to U.S. GAAP-based numbers. This study applies accounting-based valuation models by using these two sets of accounting numbers. The valuation error, defined as the difference between the market value of the firm and its intrinsic values calculated by the valuation models, serves as the benchmark of the usefulness of the accounting system for its users in their decision making. The findings of this study, using companies whose Form 20-F are based on International Accounting Standards (IAS) and/or Australian GAAP, suggest that both IAS and Australian GAAP have smaller bias in valuation than U.S. GAAP. However, the valuation errors are more widely dispersed with non-U.S. GAAPs. This is consistent with the SEC's call for tighter implementation of IAS. Results from the second sample suggest that translating Japanese GAAP into U.S. GAAP increases the usefulness of accounting numbers, which supports ongoing restructuring of Japanese accounting standards.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

A Comparative Study of the Usefulness of Accounting Systems

100 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2001.The main purpose of this study is to test whether the U.S. accounting system is more useful than other accounting systems in estimating firms' value by using a new method of comparing alternative accounting systems. This method examines whether one accounting system is superior to another accounting system with its ability to correctly measure a firm's worth, represented by the prevailing market price of its stock. Specifically, the analysis employs accounting-based valuation models developed by Ohlson (1995) and extended by Penman (1997). Two sets of sample are used in this study. The first sample consists of non-U.S. firms that report in Form 20F. These firms usually provide two different financial statements, one by their 'home' Generally Accepted Accounting Principles (GAAP) and the other by U.S. GAAP. The second sample consists of Japanese firms that are listed on at least one of the stock exchanges in Japan and that prepare consolidated financial statements on Japanese GAAP. For this sample, attempts are made to translate Japanese-GAAP based numbers to U.S. GAAP-based numbers. This study applies accounting-based valuation models by using these two sets of accounting numbers. The valuation error, defined as the difference between the market value of the firm and its intrinsic values calculated by the valuation models, serves as the benchmark of the usefulness of the accounting system for its users in their decision making. The findings of this study, using companies whose Form 20-F are based on International Accounting Standards (IAS) and/or Australian GAAP, suggest that both IAS and Australian GAAP have smaller bias in valuation than U.S. GAAP. However, the valuation errors are more widely dispersed with non-U.S. GAAPs. This is consistent with the SEC's call for tighter implementation of IAS. Results from the second sample suggest that translating Japanese GAAP into U.S. GAAP increases the usefulness of accounting numbers, which supports ongoing restructuring of Japanese accounting standards.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD