biology

Diabetes
medicine

Photo Credit: ©sxc.hu/Mike Hughes

and
Calcineurin
by Chelsea Young

A Single Protein
May Treat The Symptoms of Diabetes
“The cause of diabetes continues to be a mystery,” states When insulin does not fulfill its function in diabetes, the
the American Diabetes Association (ADA) on its website. body’s cells begin to starve from lack of glucose. In Type
However, Stanford Medical School Professors Seung Kim I diabetes, insulin production slows down or stops due to
and Gerald Crabtree, along with MD/PhD graduate student malfunctioning beta cells. In Type II diabetes, the beta cells
Jeremy Heit, are closer to solving this mystery. They recently still produce insulin, but the body’s cells develop a resistance
singled out a specific protein that controls the disease’s
symptoms -- a finding that could potentially lead to an
effective cure for 20.8 million Americans - 7% of the U.S. They recently singled out a specific
population.
protein that controls [diabetes]
An Insulin Disease
After eating a meal, a person’s blood sugar level rises. Beta symptoms.
cells, located in the pancreas, sense this increase in glucose
and release insulin into the body. Insulin is a hormone that
induces cells in the muscles and liver to absorb and store the to it. In both cases, continually high levels of sugar in the
glucose as the body’s energy source. blood can lead to long-term problems such as blindness,
kidney failure and nerve damage.

Searching for the Cause

Kim, winner of the ADA’s Career
Development Award, and Heit decided to
Photo Credit: Human Genome Program, U.S. Dept. of Energy, Human Genome News (v12n1-2)

explore the mechanisms behind diabetes after

noticing that up to thirty percent of patients
taking the common immunosuppressant drugs
tacrolimus and cyclosporin A, which inhibit
calcineurin - a protein involved in immune
response activation - also developed diabetes
as a side-effect. Reducing the patients’ drug
dosages tended to get rid of the disease. Based
on their findings, the pair hypothesized that
calcineurin is somehow inactivated in diabetes
as well.
With help from Crabtree, Kim and Heit’s
team deleted the calcineurin gene in mice
beta cells, and as expected, these mice quickly
developed diabetes. Upon closer examination,
the researchers deduced that calcineurin was
The molecular structure of the protein calcineurin. necessary for beta cell proliferation, as well

28 stanford scientific
 biology
asthe production and secretion of insulin. Furthermore, As always, even with such positive research +
medicine
they determined that these three functions were controlled results, patients today may never experience
by six genes, all of which had low levels of expression in the the benefits of a drug based on these findings.
absence of calcineurin. Heit estimates that the development, testing and
However, further investigation revealed that calcineurin marketing of such a drug will take “probably ten to twenty
was not directly responsible for normal beta cell function. years, but maybe faster if other people start to investigate
Instead, calcineurin activates a protein called Nfat (nuclear this line of thought along with us.” While human studies
factor of activated T-cells), which in turn activates the six and clinical trials will inevitably lead to some obstacles, Kim,
genes. When the team Crabtree and Heit have taken
activated Nfat in the a huge step toward making
calcineurin-deficient mice, “These data suggest that diabetes a problem of the
beta cell function was past. S
restored and the diabetes mutations in calcineurin or Nfat or
symptoms disappeared.
“These data suggest that
other components of the signaling CHELSEA YOUNG is a sophomore ma-
mutations in calcineurin or
Nfat or other components
pathway they function in may joring in biological sciences. She
also enjoys running, reading and
of the signaling pathway be responsible for some forms of eating chocolate.
they function in may be
responsible for some forms human diabetes, which is a new
of human diabetes, which
is a new finding,” explained finding.” - Heit Below: A woman tests her
blood sugar level with a dia-
Heit. The researchers betes kit.
published their findings in
the September 21st issue of Nature.

From Lab to Countertop

If it can be proven that calcineurin acts in humans as

Photo Credit: ©sxc.hu/Karen Barefoot

it does in mice, its potential for therapeutic applications
is tremendous. For instance, Kim also studies beta cell
implantation for patients with Type I diabetes. After
implantation, these patients must take immunosuppressant
drugs that decrease calcineurin function. If Nfat activators
could be introduced into the patients’ systems, via gene
therapy prior to transplantation, then lifelong diabetes
sufferers could experience a complete cure.
Photo Credit: ©sxc.hu/Dain Hubley

To Learn More:

Visit the Kim Lab website:

http://seungkimlab.stanford.edu/

Read ”Calcineurin/NFAT signaling regulates

pancreatic ß-cell growth and function” in
Nature: J.J. Heit, Å.A. Apelqvist, X. Gu, M.M.
Winslow, J.R. Neilson, G.R. Crabtree and S.K.
Kim. 2006.

Diabetics must carefully monitor their sugar intake to avoid dangerously high blood glucose levels.

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