Bacterial Regulation of Host Pancreatic Beta Cell Development

Diabetes is a metabolic disease characterized by the loss of functional pancreatic beta cells. The incidence of diabetes has risen rapidly in recent decades, which has been attributed at least partially to alterations in host-associated microbial communities, or microbiota. It is hypothesized that t...

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Bibliographic Details
Main Author: Hill, Jennifer
Other Authors: Guillemin, Karen
Language:en_US
Published: University of Oregon 2018
Subjects:
Online Access:http://hdl.handle.net/1794/23140
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spelling ndltd-uoregon.edu-oai-scholarsbank.uoregon.edu-1794-231402019-01-06T05:41:28Z Bacterial Regulation of Host Pancreatic Beta Cell Development Hill, Jennifer Guillemin, Karen BefA Beta cells Development Diabetes Microbiota Zebrafish Diabetes is a metabolic disease characterized by the loss of functional pancreatic beta cells. The incidence of diabetes has risen rapidly in recent decades, which has been attributed at least partially to alterations in host-associated microbial communities, or microbiota. It is hypothesized that the loss of important microbial functions from the microbiota of affected host populations plays a role in the mechanism of disease onset. Because the immune system also plays a causative role in diabetes progression, and it is well documented that immune cell development and function are regulated by the microbiota, most diabetes microbiota research has focused on the immune system. However, microbial regulation is also required for the development of many other important tissues, including stimulating differentiation and proliferation. We therefore explored the possibility that the microbiota plays a role in host beta cell development. Using the larval zebrafish as a model, we discovered that sterile or germ free (GF) larvae have a depleted beta cell mass compared to their siblings raised in the presence of bacteria and other microbes. This dissertation describes the discovery and characterization of a rare and novel bacterial gene, whose protein product is sufficient to rescue this beta cell developmental defect in the GF larvae. Importantly, these findings suggest a possible role for the microbiota in preventing or prolonging the eventual onset of diabetes through induction of robust beta cell development. Furthermore, the loss of rare bacterial products such as the one described herein could help to explain why low diversity microbial communities are correlated with diabetes. 2018-04-10T15:02:35Z 2018-04-10 Electronic Thesis or Dissertation http://hdl.handle.net/1794/23140 en_US All Rights Reserved. University of Oregon
collection NDLTD
language en_US
sources NDLTD
topic BefA
Beta cells
Development
Diabetes
Microbiota
Zebrafish
spellingShingle BefA
Beta cells
Development
Diabetes
Microbiota
Zebrafish
Hill, Jennifer
Bacterial Regulation of Host Pancreatic Beta Cell Development
description Diabetes is a metabolic disease characterized by the loss of functional pancreatic beta cells. The incidence of diabetes has risen rapidly in recent decades, which has been attributed at least partially to alterations in host-associated microbial communities, or microbiota. It is hypothesized that the loss of important microbial functions from the microbiota of affected host populations plays a role in the mechanism of disease onset. Because the immune system also plays a causative role in diabetes progression, and it is well documented that immune cell development and function are regulated by the microbiota, most diabetes microbiota research has focused on the immune system. However, microbial regulation is also required for the development of many other important tissues, including stimulating differentiation and proliferation. We therefore explored the possibility that the microbiota plays a role in host beta cell development. Using the larval zebrafish as a model, we discovered that sterile or germ free (GF) larvae have a depleted beta cell mass compared to their siblings raised in the presence of bacteria and other microbes. This dissertation describes the discovery and characterization of a rare and novel bacterial gene, whose protein product is sufficient to rescue this beta cell developmental defect in the GF larvae. Importantly, these findings suggest a possible role for the microbiota in preventing or prolonging the eventual onset of diabetes through induction of robust beta cell development. Furthermore, the loss of rare bacterial products such as the one described herein could help to explain why low diversity microbial communities are correlated with diabetes.
author2 Guillemin, Karen
author_facet Guillemin, Karen
Hill, Jennifer
author Hill, Jennifer
author_sort Hill, Jennifer
title Bacterial Regulation of Host Pancreatic Beta Cell Development
title_short Bacterial Regulation of Host Pancreatic Beta Cell Development
title_full Bacterial Regulation of Host Pancreatic Beta Cell Development
title_fullStr Bacterial Regulation of Host Pancreatic Beta Cell Development
title_full_unstemmed Bacterial Regulation of Host Pancreatic Beta Cell Development
title_sort bacterial regulation of host pancreatic beta cell development
publisher University of Oregon
publishDate 2018
url http://hdl.handle.net/1794/23140
work_keys_str_mv AT hilljennifer bacterialregulationofhostpancreaticbetacelldevelopment
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