(Ivanhoe Newswire) — Crack open the latest medical textbook to the
chapter on type 2 diabetes and you'll be hard pressed to find the term
"immunology" anywhere. Metabolic conditions and immunologic conditions are,
with a few exceptions, thought to be distant cousins. Recent studies,
however, two of which are from Harvard Medical School researchers, have
linked type 2 diabetes with immunology in a way that might persuade
researchers to start viewing them as siblings.
Type 1 and type 2 diabetes both involve abnormalities in the
insulin-producing beta cells of the pancreas, but their root causes are
completely different. Type 1 diabetes is an autoimmune disease in which the
immune system attacks the pancreas, destroying its ability to produce
insulin. Type 2 diabetes is a strictly metabolic condition in which cells
grow increasingly deaf to insulin signals and thus lose their ability to
metabolize glucose. In both cases, blood glucose levels rise, sometimes to
fatal levels.
Researchers used two common over-the-counter allergy medications to reduce
both obesity and type 2 diabetes in mice. The medications, called Zaditor
and cromolyn, stabilize a population of inflammatory immune cells called
mast cells.
The Harvard researchers assert that it is becoming increasingly clear that
we should also think of type 2 diabetes in the context of immune function.
Guo-Ping Shi, biochemist from the Department of Medicine, Brigham and
Women's Hospital and Harvard Medical School, began to suspect such a
connection when, in a previous study, he found mast cells present in a
variety of inflammatory vascular diseases.
Mast cells are immune cells that facilitate healing in wounded tissue by
increasing blood flow to the site. In certain conditions, however, mast
cells build up to levels far beyond what the body needs. When this happens,
these cells become unstable and eventually, like punctured trash bags, leak
molecular "garbage" into the tissue. This results in chronic inflammation
that can cause asthma and certain allergies.
As Shi and postdoctoral research fellow Jian Liu discovered, mast cells were
far more abundant in fat tissue of obese and diabetic humans and mice than
they were in fat tissue from individuals of normal weight. This led to the
obvious question, by regulating mast cells, could we then control the
obesity and diabetic symptoms?
To find out, Shi and colleagues took a group of obese and diabetic mice and,
for a period of two months, treated them with either Zaditor or cromolyn.
The mice were divided into four groups. The first was the control group. The
second group was simply switched to a healthy diet. The third was given
cromolyn or Zaditor. And the fourth group was given the drug and switched to
a healthy diet.
While symptoms of the second “healthy diet” group improved moderately, the
third “allergy medicine” group demonstrated dramatic improvements in both
body weight and diabetes. The fourth group exhibited nearly 100 percent
recovery in all areas.
To bolster these findings, Shi and colleagues then took a group of mice
whose ability to produce mast cells was genetically impaired. Despite three
months of a diet rich in sugar and fat, these mice neither became obese nor
developed diabetes. "The best thing about these drugs is that we know it's
safe for people," said Shi. "The remaining question now is: Will this also
work for people?" Shi now intends to test both cromolyn and Zaditor on obese
and diabetic non-human primates.
SOURCE: Nature Medicine, July 26, 2009
