October 18, 2001
Bigger Betas Are Better - Protein
Found To Provide Pancreatic Cells with Protection against
Diabetes
(Philadelphia,
PA) -While studying the proteins in pancreatic beta
(b) cells - the cells that produce insulin - researchers
at the University of Pennsylvania Medical Center discovered
how the protein enzyme Akt1 can cause mice b cells to
grow larger and produce more insulin. Their findings,
published in this month's Nature Medicine, have direct
implications for the current need to increase the number
of human pancreatic cells available for transplant to
diabetic patients.
"The mice bred to produce excess Akt1 protein were
more tolerant of glucose and more resistant to diabetes
- in fact, we simply could not give them diabetes when
we tried," said Morris J. Birnbaum, MD, PhD,
associate director of the Penn Diabetes Center
and professor in the Penn Department of Cell &
Developmental Biology and an investigator in the
Howard Hughes Medical Institute. "The increase
in Akt1 directly leads to an increase in the size, amount,
and total production of insulin by b cells."
In the United States, diabetes is the seventh leading
cause of death and currently effects over 15 million
people. Medical science recognizes two forms of diabetes.
Type 1 diabetes results from the immune system's destruction
of pancreatic b cells. Type 2 diabetes results when
the body cannot either produce enough insulin or properly
use the insulin it does produce. Without insulin, the
body cannot utilize glucose - blood sugar - which can
lead to a variety of debilitating illnesses, including
heart disease, blindness, and kidney failure.
Recently, surgeons have met with success in treating
the disorder by transplanting clusters of pancreatic
cells, called islets, into diabetic patients. Transplanted
islets, which include b cells, have been shown to reestablish
the production of insulin in the pancreas. Unfortunately,
the demand for islets far outweighs the supply.
"What makes our findings so interesting, clinically,
is the potential to enlarge our pool of b cells for
transplant," said Birnbaum. "We see that Akt1
causes more plentiful, and bigger, b cells - they are
plump, well fed cells."
The Penn research team, spearheaded by graduate student
Robyn Tuttle, began this study to look specifically
at the role of Akt1 in living organisms in order to
evaluate the protein's possible role in the b cell loss
that causes diabetes. Previously, studies of Akt1 in
cell cultures determined that the protein had an important
role in assisting the function of insulin and helping
cells convert glucose into energy. After failing to
induce diabetes in their experimental mice by killing
b cells, Birnbaum and his colleagues found that there
was a significant increase in both b cell size and the
total mass of the islets.
According to Birnbaum, Akt1 is a potent factor in deciding
the size of cells in mammals. One view is that insulin
signaling through Akt1 leads to a coordinated increase
in cellular metabolism, which results in bigger cells
and an increase in the amount of proteins the cells
make. The interplay between insulin and glucose is,
in essence, the story of how our bodies derive energy
from the food we eat. The Akt1 protein has an important,
behind-the-scenes, role in putting that story in motion
and coordinating the events.
Perhaps what has surprised the researchers most is how
they also see evidence that Akt1 promotes the creation
of entirely new b cells.
"The number of b cells that you will have at any
given time are determined by three things: how fast
they divide, how fast they die, and how fast your body
can generate completely new ones," said Birnbaum.
"Since the death rate and the division rate did
not change in our mice, it is possible that Akt1 also
promotes the growth of new b cells."
Funding for this research was provided by the National
Institutes of Health.
# # #
The University of Pennsylvania Health System is distinguished
not only by its historical significance - first hospital
(1751), first medical school (1765), first university
teaching hospital (1874), first fully integrated academic
health system (1993) - but by its position as a major
player on the world stage of medicine in the 21st century.
Committed to a three-part mission of education, research,
and clinical excellence, UPHS has excelled in all three
areas. Penn ranked second among all American medical
schools that received funds from the National Institutes
of Health, perhaps the single most important barometer
of research strength.
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