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ADDITIONAL^ PHOTOGRAPHY^GETTY^IMAGES“We know that people who are
overweight are prone to type
2 diabetes,” explains Associate
Professor Schmitz-Peiffer. “What
we’ve now proven is that a specific
enzyme that is known to drive
diabetes is activated by obesity.”
This enzyme – protein kinase
C epsilon (PKC) – has long been
known to be involved in the
generation of type 2 diabetes.
The surprising finding researchers
made was that this enzyme isn’t
acting in the liver, which has been
assumed for at least a decade.Previous research had
established that mice which do not
produce PKC at all will not develop
diabetes-like symptoms – even
under conditions where other
mice become diabetic.
What Garvan’s world-first
research uncovered was that
inhibiting PKC production
specifically in the liver did not
protect the mice from becoming
glucose intolerant. However,
stopping PKC production in fat
tissue protected the mice.
“When we closely examinedfat tissue, we
realised there is a
striking difference
in the shape and size
of fat cells, depending
on whether PKC is
present,” says Associate
Professor Schmitz-Peiffer. “The
results in mouse models suggest
PKC is acting from fat tissue to
worsen the disease. When it’s
chronically activated in obesity, it
most likely alters the communication
with liver and muscle and so reduces
the proper storage of glucose.”Understanding fat
New research has further
highlighted an enzyme’s
role in diabetes, demonstrating
that it works in fat. Now,
scientists are homing in on
a way to block its function.
Most of us think of our fat
tissues as where we store energy
(whether we like it or not), but
growing evidence is revealing
that fat is a dynamic endocrine
organ that sends messages
throughout the body. The nature
of fat cells, and how they change,
could have wide-ranging, complex
implications for type 2 diabetes.
This recent discovery by
researchers from the Garvan
Institute of Medical Research,
throws into doubt the traditional
definition of diabetes as a disease
of the pancreas, muscle and liver.
Due to the decline in the
body’s reaction to insulin, type
2 research has generally focused
on the pancreas (which produces
insulin) and muscle and liver
(because of their roles in storing
and releasing blood sugar).
However, the breakthrough
discovery from Garvan’s
Associate Professor Carsten
Schmitz-Peiffer (pictured above
right) is that an enzyme in fattissue is another important
driver in diabetes.Target for a treatment
What the science also highlighted
is the significant role the PKC
enzyme plays as a driver of the
disease, which identifies it as a
prime target for a new way to
treat diabetes.
Garvan researchers are now
collaborating with the Monash
Institute of Pharmaceutical
Sciences to develop a drug that
will specifically target and block
the enzyme. “By blocking PKC
function, we hope to improve
the body’s insulin action, as
well as the controlled release
of insulin by the pancreas,
to have a two-fold impact,”
Associate Professor Schmitz-
Peiffer explains, emphasisingthe need for the drug to act only
on the target enzyme.
“Because diabetes is a
chronic disease and we know
that people could be on this
medication for a lifetime, it
has to be extremely specific
in blocking this enzyme while
not causing off-target effects.”
This new approach to treating
diabetes is still in vitro, meaning
it’s early days. “We’ve had very
encouraging ‘screening hits’
and are now tweaking these
molecules and will be testing
them in cell models,” Associate
Professor Schmitz-Peiffer says.
The course of drug
development is a slow and
methodical process.
When researchers are able to
produce a drug that is potent
and selective enough, they will
progress to animal tests and
then, if all goes according to
plan, human clinical trials.
In the meantime, for those who
are overweight or obese and are
impacted by type 2, the findings
also indicate that losing weight
through a healthy diet and
exercise plan should
still be on your
radar. ■diabetic living MARCH/APRIL 2019 113