Some cases of diabetes are caused by mutations to a single gene, In studies of such cases, a team of Washington University researchers has identified the way that those genetic mutations cause problems. Although most people with the genetic form of diabetes called Mature-Onset Diabetes of the Young 1, seem to have clinical symptoms that are very close to the symptoms that affect people with type 2 diabetes, these studies show that the underlying mechanisms are very different. Most treatments for type 2 diabetes are designed to excite insulin-secreting cells into making more insulin, but thats not the problem in the genetic form of the disorder. The study finds that insulin-secreting cells are under stress in the genetic form of diabetes, and those treatments that work in type 2 diabetes can increase stress, eventually killing the cells. So the researchers say say their findings suggest that patients with that genetic form of diabetes may need a different type of therapy.
ALMOST 30 MILLION AMERICANS HAVE DIABETES, AND THE VAST MAJORITY HAVE THE NON-INSULIN-DEPENDENT FORM OF THE DISORDER, CALLED TYPE 2. BUT UP TO 5 PERCENT OF THOSE WITH DIABETES HAVE A FORM THATS CAUSED BY CHANGES IN A SINGLE GENE. AND NOW, RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE UNCOVERED THE MECHANISM THAT CAUSES THOSE PATIENTS TO BECOME DIABETIC, AND THEIR FINDINGS SUGGEST THAT MANY WHO HAVE THE GENETIC FORM OF DIABETES MAY NEED A DIFFERENT TYPE OF THERAPY THAN WHAT THEYRE GETTING CURRENTLY. JIM DRYDEN HAS MORE
THE GENETIC FORM OF DIABETES IS CALLED MATURE-ONSET DIABETES OF THE YOUNG, OR MODY. PATIENTS WITH THAT FORM OF THE DISORDER OFTEN ARE NOT DIAGNOSED BECAUSE THEY HAVE SYMPTOMS THAT LOOK A LOT LIKE THOSE SEEN IN PATIENTS WITH TYPE 2 DIABETES, ACCORDING TO RESEARCHER BEN MOORE.
(act) :12 o/c years old
Theyre really not often detected because they present a lot
like type 2 diabetes. So they look like type 2 diabetes, but
they happen uncharacteristically young. So they happen between
15 and 25 to 35 years old.
WORKING IN THE LABORATORY OF WASHINGTON UNIVERSITY RESEARCHER JASON MILLS, MOORE DISCOVERED A PAIR OF PROTEINS THAT FUNCTION DIFFERENTLY TO GIVE PATIENTS THE MODY FORM OF DIABETES. THE GENES THAT MAKE THOSE PROTEINS ARE CALLED TRANSCRIPTION FACTORS, WHICH ARE THE SORTS OF GENES EVENTUALLY ASSOCIATED WITH MANY OTHER GENES. IN THIS CASE, MOORE SAYS, WHEN THE TRANSCRIPTION FACTORS BEHAVE A CERTAIN WAY, THE RESULT IS LOTS OF STRESS FOR INSULIN-SECRETING BETA CELLS IN THE PANCREAS.
(act) :21 o/c the pancreas
And the way that these transcription factors interact with
each other can make effect huge changes in the way that a cell
functions and behaves. And weve identified a relationship
between two transcription factors that is necessary for the
proper function of cells that secrete insulin in the pancreas.
AND UNFORTUNATELY, SINCE THE CLINICAL SYMPTOMS OF THE DISEASE LOOK SO MUCH LIKE THOSE IN TYPE 2 DIABETES, DOCTORS USUALLY TREAT PATIENTS WITH THE SAME TYPE OF MEDICATION THAT THEY GIVE TO TYPE 2 PATIENTS. THE PROBLEM WITH THAT IS THE MEDICINE IS DESIGNED TO EXCITE INSULIN-SECRETING BETA CELLS, WHICH PUTS THEM UNDER EVEN MORE STRESS AND APPARENTLY KILLS THEM OVER TIME. WHAT SHOULD BE TARGETED, SAYS SENIOR INVESTIGATOR JASON MILLS, IS THE TRANSCRIPTION FACTOR CALLED HNF4-ALPHA, A GENE THAT THEY IDENTIFIED WHILE STUDYING OF THE DEVELOPMENT OF CELLS IN THE STOMACH. MILLS SAYS IT APPEARS A LOT OF CELLS THAT SECRETE THINGS LIKE BETA CELLS, STOMACH CELLS, AND LIVER CELLS MAY RELY ON THE SAME HNF4-ALPHA MACHINERY.
(act) :18 o/c same approach
Obviously, what they secrete is incredibly important and different.
The factories for building a BMW are not really that different from
the factories for building a Volkswagen. The end product is, of
course, incredibly important what the difference is, but actually,
all the machinery you need is relatively similar. And it seems like
nature has that same approach.
AND MOORE SAYS AS A RESULT OF THE DISCOVERIES, IT APPEARS TO BE A GOOD IDEA FOR DOCTORS TO TEST FOR IRREGULARITIES IN HNF4-ALPHA SO THAT THEY CAN MAKE SURE THEYRE NOT SIMPLY TREATING PATIENTS WITH THE MODY FORM OF DIABETES AS IF THEY HAD THE MORE COMMON TYPE 2 FORM.
(act) :11 o/c that pathway
Weve identified a completely different pathway that is disrupted
in MODY not the same thing that is disrupted in type 2 diabetes.
So hopefully this will lead to further research kind of uncovering
drugs that are able to modulate that pathway.
THE NEW STUDY IS PUBLISHED IN THE JOURNAL OF BIOLOGICAL CHEMISTRY. IM JIM DRYDEN…