AUTHOR=Petry Sebastian Friedrich , Sun Lia Mingzhe , Knapp Anna , Reinl Sabrina , Linn Thomas 

TITLE=Distinct Shift in Beta-Cell Glutaredoxin 5 Expression Is Mediated by Hypoxia and Lipotoxicity Both In Vivo and In Vitro

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00084

DOI=10.3389/fendo.2018.00084

ISSN=1664-2392

ABSTRACT=Histomorphological and functional alterations in pancreatic islet composition directly correlate
with hyperglycemia severity. Progressive deterioration of metabolic control in subjects suffering
from type 2 diabetes is predominantly caused by impaired beta-cell functionality. The glutaredoxin
system is supposed to wield protective properties for beta-cells. Therefore, we sought to
identify a correlation between the structural changes observed in diabetic pancreatic islets
with altered glutaredoxin 5 expression, in order to determine an underlying mechanism of betacell
impairment. Islets of db/db mice presenting with uncontrolled diabetes were assessed in
terms of morphological structure and insulin, glucagon, and glutaredoxin 5 expression. MIN6 cell
function and glutaredoxin 5 expression were analyzed after exposure to oleic acid and hypoxia.
Islets of diabese mice presented with typical remodeling and were marked by distinct reduction
of, and shifts, in localization of glutaredoxin 5-positive cells. These islets featured decreased
glutaredoxin 5 as well as insulin and glucagon content. In beta-cell culture, glutaredoxin 5 protein
and mRNA expression were decreased by hypoxia and oleic acid but not by leptin treatment.
Our study demonstrates that glutaredoxin 5 expression patterns are distinctively altered in islets
of rodents presenting with uncontrolled diabesity. In vitro, reduction of islet-cell glutaredoxin 5
expression was mediated by hypoxia and oleic acid. Thus, glutaredoxin 5-deficiency in islets
during diabetes may be caused by lipotoxicity and hypoxia.