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Kade Edsall
Professor Salgat
ENG 111-02
15 November 2014
Using the Gut to Cure Diabetes
There are approximately 1.5 million people in the United Sates who have type one
diabetes (Targeted News Service). Some do not know that there is more than one type of
diabetes. In type one diabetics there is no insulin being made or used whereas type two there is
some being made or possibly just not all being absorbed. There is also gestational diabetes which
occurs in pregnant women. It normally ceases after birth but gives the mother and the child a
greater chance for type two diabetes later in life. Type one is more common in children which is
why it is also called juvenile diabetes and is passed down from genetics, and type two is more
common in people who are older that normally do not have good diet and exercise habits but it is
more likely to occur in a family that has diabetes of either type in the family history. Although
one of the most predominant differences is that with type two the patient can take a once daily
pill and that once it is taken and diet and exercise is managed. Type one cannot be so easily
controlled. It takes day in and day out treatment. Checking blood glucose levels as many as eight
times per day as well as numerous insulin injections. If neglected for even one day the cycle for a
type one diabetic can spiral out of control leading to diabetic ketoacidosis or DKA from
hyperglycemia or too high of a blood glucose level. If left untreated for too long the effects from
DKA can be catastrophic, starting with indigestion, heartburn, and drowsiness, leading all the up
to severe dehydration, hallucinations, and even coma. (American Diabetes Association). There is

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also hypoglycemia in which the blood glucose goes too low and the effects of that can be as
simple as hunger, excessive sweating, or pale skin, all the way to slurred speech, loss of
consciousness, inability to swallow, and even seizures (American Diabetes Association). The
long term of diabetes can also be very tragic. The loss of limbs, erectile dysfunction, and
possibly renal failure which can lead to death if dialysis or a transplant is not an option. There
are various treatment options for type one diabetics. Syringes, pre filled pens, and pumps. All of
these treat for the time being but as of this day and age there has been no cure for diabetes. Some
of the things that have been attempted and tested are, pancreas transplant in which the survival
and success rate are both extremely low and there is a risk that the transplanted organ will not
work and the person will still have diabetes. The use of stem cells is also quite risky with named
complications. There is also the use of gut cells in which the gut cells are used and transformed
into making insulin which is a kind of hormone. Making hormones is a job the gut cell already
does in the first place. Use of gut cells is the most effective and safest ways to potentially cure
type one diabetes. This disease is said by Drug Discovery to, [have] 30,000 newly diagnosed
cases a year a figure that is rising by approximately four percent annually (Nature Reviews).
That would be the equivalent of nearly the entire population of Bay City, Michigan having
diabetes.
Gut cells are found in nearly every man, woman, and child on Earth. They are used by the
body to make different kinds of hormones. It has been found that the FOX01 cell, when turned
off by means of genetic engineering, After seven days, some of the cells started releasing
insulin and, equally important, only in response to glucose (Accili). The same study was done in
mice with diabetes. The insulin made by the gut cells almost completely normalized the mices
blood glucose levels that were otherwise high due to the diabetes. Dr. Accili had this to say about

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the discovery, By showing that human cells can respond in the same way as mouse cells, we
have cleared a main hurdle and can now move forward to try to make this treatment a reality

(Accili).
Since this testing Dr. Accili is attempting to find a drug that will inhibit the FOX01
gastrointestinal cell in people. There is a much lesser chance of the body reacting negatively to
this treatment as well because the immune system defense that attack the pancreas cells that
create insulin will not attack the insulin creating gut cells because of where they are in the body.
The treatments used today for type one diabetes work but they are simply not a cure. The
methods are a constant check and balance process. There is a lot of stress involved in taking care
of ones self especially when a teen or child has it. There is a constant mental struggle between
not wanting to have the disease and having to keep it in check so that it does not go out of
control. Even when it is controlled to the best of ones ability only so much can be done and it
does not ensure that down the road there will not be complications. The complications can
include everything from eye damage or retinopathy which can lead to blindness, and high blood
pressure, to stroke, neuropathy causing numbness in the feet, as well as kidney disease, and
hyperosmolar hyperglycemic nonketotic syndrome or HHNS, a condition that start out with

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dehydration and progressively worsens as time goes without treatment for it and can potentially
lead to seizures and coma and eventually death. The only way to try and prevent these from
happening from diabetics is to cure diabetes. The standard treatment of type one diabetes is that
the person who was the disease is to have them prick their finger countless times a day as well as
taking several shots per day. There is insulin pump therapy, in which one only has to change the
site of insertion every three days, but that does not ensure an event of hypoglycemia not
happening, more commonly called a low. There are also continuous blood glucose monitoring
systems, which can synchronize to the users insulin pump but, the use of a lancet and regular
blood glucose meter are still used to compare and contrast the levels from each device and decide
what is the best to use for the user. The only real way to prevent these awful things from
happening is to cure the disease altogether instead of just treating a high or a low blood glucose.
Unfortunately the only thing remotely close to a cure is just treating it as of today.
Stem cells have been considered as a cure for diabetes as has it been for many other
diseases and conditions. Although it seems like stem cells have been the cure for nearly
everything, there are underlying risks involved. One source claims that after the stem cell
transplant, 25 years after the cumulative incidence of arterial events was 22% (Green). This
means the 25 years after finishing the operation, assuming the patients makes it through and their
body does not reject the new organ, the chance of having a heart attack went up 22%. Not to
mention one who does keep their pancreas would need to take immune system depressants to
make sure their immune system does not attack the new insulin producing cells that have just
been transplanted. The theory behind using stem cells is that it could be used to create new
pancreatic cells to create insulin, but even figuring in that one finds compatible stem cells and
the transplant goes well there is still a likelihood that the bodys immune system will attack the

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new pancreas and the insulin will not be created efficiently. Stem cells are an extremely
expensive and highly risky way to go about treating diabetes as are all transplants.
Pancreatic transplant is another option. Pancreatic transplant although seems like a viable
solution not many of them are successful, with very high rejection rates. The only time a
pancreatic transplant s really considered an option is when the patient has renal or kidney failure
and could possibly die without transplantation anyway. When it comes down to this, it cannot
hurt if the patient undergoes this type of surgery because although they might not make it after
the surgery the chances of morbidity without the surgery would most certainly not have let them
live any longer. By doing the surgery they do have a slightly better chance at surviving longer.
Even though these procedures are minimally invasive, up to 35% of recipients of SPK might not
survive for 10 years to have these benefits (White, Shaw and Sutherland). SPK being
simultaneous pancreas and kidney transplant. The only real reason one would have SPK is that
they did have renal failure from lack of caring for their diabetes or even just complications from
having the disease for so long. But that leaves there being not a sensible option as far as
transplant that is not just a last option. Even the few patients that do survive these transplants
have the chance of becoming type one diabetic again. When the transplant does work and the
body does not reject it and the procedure goes as planned, the bodys immune system can still
attack the beta cells responsible for creating insulin which put the patient exactly where they
started not to mention having surgery bills. The studies showed that:
Insulin secretion became impaired and hyperglycemia [requiring] insulin therapy ensued
5 (patient 1), 9 (patient 2), and 5 (patient 3) years after transplantation, respectively. They
maintained normal exocrine pancreas graft function (secretion of urine amylase) and normal

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kidney graft function throughout the follow-up, even beyond the time of diabetes recurrence.
Thus, the patients had no clinical signs of rejection. (Vendrame, Pileggi and Laughlin)
There are drugs in development that are supposed to help cure diabetes. One of the senior
Research Fellows at Lilly had this to say about the drugs being engineered for type one diabetes,
Tolerogenic drugs re-establish tolerance to autoantigens by suppressing or inactivating
pathogenic autoreactive T cells, in a sense, these drugs re-establish the equilibrium between
autoreactive T cells and T regulatory cells that has become disrupted (Nature Reviews). In
essence this drug would be an immune system depressant. This would potentially lead to people
becoming deathly sick from things that otherwise their bodies would be able to defend
themselves from. With an immunodepressant the bodys white blood cells do not attack as
efficiently against incoming illnesses such as the common cold or the flu, which can be lethal to
diabetics in the first place. In the words of Richard Insel, Executive Vice President of Research
at the Juvenile Diabetes Research Foundation (JDRF), We need to address the underlying
immune response that caused the disease in the first place, and restore beta cell function, to
create a cure (Nature Reviews). This can be done by means of inhibition of the FOX01 cell to
start creating new insulin producing cells.
Diabetes is a disease that no person should ever have to live with. No matter how easy it
might be today with insulin pumps there is still not a cure. FOX01 cell therapy is the way that a
cure for diabetes is leaning towards. With funding and clinical trials it is very possible that
within the next decade that there could be a cure for type one diabetes without having to subject
ones self to risky surgery, transplants, drugs that suppress the immune system so much that one
becomes susceptible to every bacteria and virus that can be found almost every day, the quality
of life for the 1.5 million Americans that have diabetes could increase drastically through one

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thing. The FOX01 gut cell that just has to be inhibited to have the body start making insulin
again all on its own and not have risk of rejection. This therapy is the way of the future and is the
way one day diabetes should be cured.

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Works Cited
Accili, Domenico. "FOX01 inhibition yields functional insulin producing cells in human gut
organoid cutures." Nature Communications 30 June 2014. Web.
Green, David. "Risk for Cardiovascular Disease After Hematopietic Stem-Cell Transplantation ."
Journal Watch. Oncology and Hematology (2012). Web.
Nature Reviews. "Retuning the immune system: the future of type 1 diabetes therapy?" Drug
Discovery (2009): 600-601. Web.
Targeted News Service. This National Diabetes Month, Take Steps To Improve Diabetes
Outcomes. 3 November 2014. Article. 7 November 2014.
Vendrame, Francesco, et al. "Recurrence of Type 1 Diabetes After Simultneou Pancreas-Kidney
Transplantation, Despite Immunodepression, Is Associated With Autoantibodies and
Pathogenic Autoreactive CD4 T-Cells." Diabetes (2010): 947-957. Web.
White, Steven, James Shaw and David Sutherland. "Pancreas Transplantation." The Lancet
(2009). Web.