Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/18227
Title: A novel sec7-domain-containing protein BIG3 and its role in regulated secretory pathway
Authors: LI HONGYU
Keywords: secretory pathway, Sec7, BIG3, insulin, beta cell
Issue Date: 26-Mar-2010
Source: LI HONGYU (2010-03-26). A novel sec7-domain-containing protein BIG3 and its role in regulated secretory pathway. ScholarBank@NUS Repository.
Abstract: The beta cell dysfunction in insulin secretion is one of the key factors in the pathophysiology of diabetes (Bell and Polonsky, 2001). However the mechanisms that underline the development of the beta cell dysfunction in humans still remain elusive. Arf-GEFs are a family of Sec7 domain proteins that regulate intracellular vesicle trafficking. BIG3 is identified as a putative member of the Sec7 protein family and distantly related to BIG/Sec7p subfamily. BIG3 mRNA expression profile shows it is selectively expressed with high levels in the brain and islet. This study therefore investigates the function of endogenous BIG3 in islet cells. BIG3 protein was found highly expressed in beta cells, and predominantly localized to the secretory granules. Investigations on BIG3 knockdown and knockout beta cells demonstrated that the deficiency of BIG3 caused increased amount of secretory granules and secretory proteins in the cells, and elevated secretion upon stimulation. The study on BIG3 knockout mice revealed that in absence of BIG3, the mice exhibited relatively elevated blood insulin level, disturbed glucose homeostasis, impaired glucose tolerance, reduced insulin sensitivity, fatty liver disease, disturbed energy expenditure and activity, and reduced testosterone level. Up-regulated insulin storage and secretion in beta cells may account for the elevated blood insulin level. The metabolic abnormalities could be in part due to the excessively secreted insulin. These data demonstrate for the first time that BIG3 has a functional role in the regulated secretory pathway to modulate the insulin secretion, and therefore to affect the whole body metabolic homeostasis.
URI: http://scholarbank.nus.edu.sg/handle/10635/18227
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Li HY HT027041R.pdf5.09 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

363
checked on Dec 11, 2017

Download(s)

286
checked on Dec 11, 2017

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.