Type

Journal Article

Authors

Lorraine O'Driscoll
Martin Clynes
Per Bendix Jeppesen
Padraig Doolan
Niall Barron
Jai Prakash Mehta
Sweta Rani

Subjects

Biochemistry

Topics
thioredoxins genetics cell proliferation insulin secreting cells rna small interfering rna messenger cell line reactive oxygen species metabolism glucose insulin animals pancreas gene expression regulation cytology gene knockdown techniques

Decreasing Txnip mRNA and protein levels in pancreatic MIN6 cells reduces reactive oxygen species and restores glucose regulated insulin secretion. (2010)

Abstract Recently, thioredoxin-interacting protein (Txnip) expression has been implicated in a number of cellular events associated with diabetes, with increased Txnip levels associated with reduced glucose uptake into peripheral tissues, increased reactive oxygen species (ROS) in endothelial cells, beta cell glucotoxicity and apoptosis. The potential relevance of Txnip with regards to glucose-regulated insulin secretion (GSIS), a fundamentally important characteristic of beta cells and insulin-producing cells being considered as a possible cell therapy for diabetes, has not yet been investigated. Here, studying glucose-responsive MIN6 B1(GSIS) and cells which had significantly reduced response to glucose after time in culture i.e. MIN6 B1(Non-GSIS), using ELISAs; qRT-PCR; immunoprecipitation and Western blotting; transient and stable (siRNA/shRNA and cDNA) approaches to achieve Txnip knock-down or over-expression, respectively,we established a direct association between Txnip expression and GSIS. Specifically, increasing Txnip levels correlate with increased intracellular ROS levels and with significant GSIS loss.Conversely, both transient and stable knock-down of Txnip expression was associated with GSIS recovery. This, we believe, is another reason in favour of targeting Txnip as a novel approach for diabetes-related therapy.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

Lorraine O'Driscoll, Martin Clynes, Per Bendix Jeppesen, Padraig Doolan, Niall Barron, Jai Prakash Mehta, Sweta Rani

Experts in our system

1
Lorraine O'Driscoll
Trinity College Dublin
Total Publications: 152
 
2
Martin Clynes
Dublin City University
Total Publications: 209
 
3
Padraig Doolan
Dublin City University
Total Publications: 37
 
4
Niall Barron
Dublin City University
Total Publications: 44
 
5
Jai Prakash Mehta
University College Dublin
Total Publications: 29
 
6
Sweta Rani
Trinity College Dublin
Total Publications: 22