Although
scientists are still working to determine what causes type 1 diabetes (T1D),
research has given us insights into the disease process – knowledge that may eventually
lead to potential therapies. One idea that has been explored over the past
several years is that of beta cell stress and its connection to T1D, and a recently
JDRF-funded study
led by the Harvard School of Public Health (HSPH) is giving us
new clues into the phenomenon and one possible way to prevent it.

Within
a cell, the endoplasmic reticulum (ER) is like a miniature factory where the
cell performs some of its specialized functions, like producing proteins. The
ER plays a crucial role in the function of pancreatic beta cells, which are
responsible for producing, storing, and releasing insulin. However, research
has shown that a component of the T1D disease process leads to ER stress,
compromising its function and contributing to beta cell death. Could reducing
cell stress and improving ER function before disease onset reduce the incidence
of T1D? This is what researchers, funded by JDRF and others, set out to
explore.

Over
the past few years, JDRF has supported research into ER stress, its causes, its
implications for T1D, and potential ways to thwart its occurrence. In 2011, a JDRF-funded study was published in Diabetes, showing for the first time evidence of beta cell stress early in the
disease process, before a clinical diagnosis of T1D. Building on this
information, the
latest piece of the puzzle is the HSPH study, published online in the November
13^th edition of Science Translational Medicine.

In
this study, Dr. Gökhan S. Hotamisligil and his team tested the effects of tauroursodeoxycholic acid (TUDCA) on ER
function in mouse models of T1D. TUDCA is a
compound that occurs naturally in animal bile, and is similar to a bile acid
that occurs naturally in humans. Previous studies by Dr. Hotamisligil’s lab
showed that ER stress in other tissues plays a significant role in obesity and
type 2 diabetes, and that it can be corrected by compounds such as TUDCA. Those
earlier findings propelled the researchers to expand their work into T1D. What
they discovered was that the application of TUDCA improved ER function in mice with T1D or pre-diabetes. Beta
cells not only functioned better but were more likely to survive, thus
preventing the onset of T1D in the animal model tested.

The HSPH study supports one of JDRF’s priority
research areas, aimed at beta cell restoration. For a decade, JDRF has funded research to explore ways to maintain
and restore the body’s ability to produce insulin and prevent the autoimmune
attack that leads to T1D. Piecing together findings from a plethora of studies
and human clinical trials will help enrich our understanding of the disease,
which will one day lead to a cure.

JDRF
is very excited by the outcome of the pre-clinical study and the potential for
developing strategies for clinical translation in people with recently diagnosed
or early stages of T1D.