Type II diabetes is one of the most researched metabolic diseases due to its increasing
prevalence in society. It is characterized by insulin resistance and β-cell failure. Studies suggest
levels of proteins such as O-GlcNAc Transferase (OGT) and proteins related to autophagy
impact insulin resistance. OGT is a post-translational protein modification enzyme that adds O-
GlcNAc to proteins to regulate cellular mechanisms and ensure homeostasis. Mice with a
decrease in β-cell OGT expression demonstrated impaired insulin secretion and a loss of β-cell
mass. Autophagy is a cellular process that breaks down dysfunctional cellular matter. It has been
implicated in playing a protective role to prevent insulin resistance by reducing oxidative stress
however it has also been proposed that an excess in autophagy leads to cell death. This study
aimed to provide a deeper understanding into the relationship between OGT and autophagy
within β-cells by using both an in vivo model and an in vitro model. βOGT-/+ mice were
compared to βOGT-/+; ULK-/+ mice with regards to glucose tolerance, plasma insulin levels,
and β-cell mass. Min6 and Ins1 cell lines were treated with STO and PUGNAc to observe the
effects of inhibiting OGT and OGA respectively. The results from these experiments suggested
that a reduction in autophagy in addition to decreased β-cell OGT expression encouraged a trend
towards better glucose control and increased insulin secretion but these changes were not the
result of a change in β-cell mass. Also, an increase in O-GlcNAcylation correlated with an
increase in expression of Beclin-1, an autophagy promoting protein, however, these findings are
not conclusive due to the lack of experimental replicates.
Effects of O-GlcNAc Transferase and Autophagy on Beta-Cell Mass and Function.
Retrieved from the University of Minnesota Digital Conservancy,
Content distributed via the University of Minnesota's Digital Conservancy may be subject to additional license and use restrictions applied by the depositor.