There is hope for a future cure of insulin-dependent (type 1) diabetes from
Jerusalem researchers who have identified the key signal that initiates
production of insulin-producing beta cells in the pancreas.
They call
their discovery a breakthrough that could help researchers find ways to restore
or increase beta cell function in people with this type of diabetes, which
usually appears in childhood.
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The work on the multi-year project was led
by Prof. Yuval Dor of the Hebrew University of Jerusalem’s Institute for Medical
Research Israel-Canada and colleagues from the Hadassah University Medical
Center, with assistance from the diabetes section of the Roche pharmaceuticals
company. The study was published in a recent issue of the journal Cell
Metabolism.
“Our work shows that as the glucose level is increased in the
blood, it tells the beta cells to regenerate,” said Dor. “It’s not blood glucose
per se that is the signal, but the glucose-sensing capacity of the beta cell
that’s the key for regeneration.”
This was the first time that this
sensing of a high level of glucose has been shown to be the “trigger” that
induces beta cells to regenerate.
In persons suffering from type 1
(juvenile-onset) diabetes, the immune system launches a misguided attack on the
insulin producing beta cells as if they were foreign cells, resulting in the
cells’ decline of insulin production and eventual loss of
function.
Without insulin, the body’s cells cannot absorb glucose from
the blood and use it for energy. As a result, glucose accumulates in the blood,
leaving the body’s cells and tissues starved for energy. That’s why people with
the disease must inject insulin and monitor their blood glucose levels carefully
several times a day. To cure type 1 diabetes, methods must be developed to
increase beta cell replication and mass, thus the potential therapeutic
importance of the current study.
In their work, Dor, along with co-lead
author Prof. Benjamin Glaser of the Hadassah University Medical Center, used a
genetic system to destroy 80 percent of the insulin-producing cells in the
pancreases of adult mice, rendering the mice diabetic.
When the
researchers compared these mice with control mice, they found that those with
diabetes and elevated blood glucose levels had regenerated a greater number of
new beta cells than mice without diabetes, suggesting that glucose may be a key
player in beta cell regeneration. They also found that a glucose-sensing enzyme
in the cells, glucokinase, is the key molecule that triggers the beta cell
regeneration.
“This means that the more work that beta cells are required
to do [that is, the more ‘stressed’ they are], the more of themselves they
make,” said graduate student Shay Porat, who, along with fellow graduate student
Noa Weinberg, spearheaded the study, which was funded with the support of the
Juvenile Diabetes Research Foundation.
Because this study showed that
regeneration depends on glucokinase levels, the finding may pave the way for
developing a new kind of drug to modulate glucokinase or other steps in the
glucose-sensing pathway to direct beta cells down the path of regeneration and
replication.
If such a mechanism that prevents the immune system from
attacking beta cells in the first place is discovered, the combined treatment
could help pave the way toward a full cure for type 1 diabetes. Further research
in this area is proceeding, with the eventual goal of progressing toward human
clinical trials.
Prof. Aaron Hanukoglu, a type 1 diabetes expert at
Wolfson Medical Center in Holon and Tel Aviv University’s Sackler Medical
School, commented: “The incidence of type 1 has been rising persistently for
several decades in many countries around the the world including Israel, and
many research groups are trying to find a cure or prevention for this chronic
disease.
This Jerusalem research on mice is very elegant and laborious,
and if proven true in humans, it may lead to development of therapeutic measures
for regeneration of pancreatic beta cells and a cure to juvenile-onset
diabetes.”
Research on animal models, Hanukoglu added, cannot always be
successfully applied in humans, and the development of therapies based on animal
studies may take many years.
“But as a pediatric endocrinologist treating
children and adolescents, I very much hope that the study results will open new
avenues for therapy,” he said.
