Is pancreas transplantation or β-cell regeneration/replacement a better option as a future cure for type 1 diabetes

Bailee Coy

SCI 291-002, Fall 2014

ABSTRACT

Pancreatic β-cells produce insulin that the human body needs to function properly, the

lack of insulin production is termed as type 1 diabetes. As of today insulin therapy is the only

means of treatment for type 1 diabetes, but increasing success with pancreas transplantation has

led to a new interest in β-cell regeneration/replacement.

β-cell regeneration/replacement could be the cure to stop the occurrence of diabetes

altogether if problems within the treatment are fixed. For both pancreas transplantation and β-cell

regeneration/replacement they require life-long immunosuppression after treatment.

INTRODUCTION

Diabetes is a disease in which the body does not produce any or enough insulin, causing

blood sugar levels in that individual to drop. There are two types of diabetes, type 1 and type 2.

Lack of insulin production due to destruction of pancreatic β-cells (insulin-producing cells) is

known as type 1 (Funnell, 2007; Gillespie, 2006; Rother and Harian, 2004). Type 2, however, is

when insulin production within the body is slowed due to obesity, physical health, gender, and

age (Rosenbloom et al., 1999). Type 2 diabetes may be treated with proper diet and exercise and

in serious cases insulin injections may be prescribed (Rosenbloom et al., 1999). As for type 1 it

is not that easy, insulin pumps, pens, and syringes are the only means of treatment as of today.

With new research on pancreas transplantation and β-cell regeneration/replacement, the

future of type 1 diabetes treatment may be changing. Pancreas transplantation is a surgical

procedure that was first introduced in 1966 (White et al., 2009). Successful pancreas transplants

restore β-cell mass to normal, therefore making insulin secretion normal again (White et al.,

2009). β-cell replacement is a procedure in which β-cells are extracted from a live brain-dead

donor pancreas and are than isolated until the replacement procedure (Ryan et al., 2002), the β-

cells are than injected by a needle the size of a catheter into the recipient (Ryan et al., 2002). For

both pancreas transplantation and β-cell replacement/replacement immunosuppression is used at

different levels to prevent rejection by the immune system (Bosi et al., 2001; Calafiore, 1997;

Gillespie, 2006; Ryan et al., 2002; White et al., 2009).

This paper will focus on more details about type 1 diabetes background information,

insulin management, why treatment and a cure is important, why pancreas transplantation would

be a better cure option for type 1 diabetes, or why β-cell regeneration/replacement would be a

better cure option for type 1 diabetes. The paper will also have photographs of an actual insulin

pump, blood sugar tester, and pancreas before transplantation.

TYPE 1 DIABETES BACKGROUND INFORMATION

Accounting for 5-10% of diabetes cases, type 1 diabetes may be less common but there is

no doubt that it is more complicated than type 2 (Rother and Harian, 2004). As said before, type

1 diabetes is due to lack of insulin production because of pancreas cell destruction (Funnell,

2007; Gillespie, 2006; Rother and Harian, 2004). The β-cell is an extremely complicated cell

within the islets of the pancreas; its main job is to produce insulin (Halban et al., 2001). The rate

of β-cell destruction may be different among different individuals, but when it reaches a critical

point (50% or more) the individual is diagnosed as type 1 diabetic (Sherry et al., 2006; and

Menge et al., 2008). Type 1 diabetes is a tricky genetic disease and for that many people go

undiagnosed for a while. It is believed that 6.2 million Americans are still undiagnosed (Funnell,

2007). This rapidly growing number makes for the unquestionable need for a cure. In earlier

years the discovery of insulin was thought to be the answer, but it was soon found that insulin

did not cure diabetes, it only helped manage it (Pickup and Renard, 2008). Insulin must be

injected by insulin syringe, pen, or pump and it was found that with its short-acting ability it was

being absorbed to slowly, making blood sugar levels unstable (Pickup and Renard, 2008). Insulin

is individualized for each specific diabetic and when injected it should be into tissue of the arm,

leg, or behind (Nath and Ponte, 2001).

Long-acting insulin and the insulin pump were introduced, and made daily insulin

management for type 1 diabetes a lot easier. The insulin pump, shown in (Figure 2), made it

possible for the diabetic individual to increase or decrease the amount of insulin they wanted

pumping throughout the day (Pickup and Renard, 2008).

Figure 2. This is an example of what an insulin pump looks like, for this particular model it holds 300 units of insulin and can continuously pump the desired amount throughout the day (photograph by author).

Insulin pumps like the one shown in (Figure 2), have a small screen that displays its functions,

buttons to increase and decrease the amount of insulin pumping, buttons to move around within

the pumps other functions, and holds 300 units of insulin. Syringes are for one time use only

(Nath and Ponte, 2001), but the insulin pump continuously delivers insulin with only a single

injection (Pickup and Renard, 2008).

With insulin being constantly pumped in at small amounts it is critical that the individual

monitors his or her blood sugar levels multiple times a day to makes sure they are stable,

unstable blood sugar levels can lead to more serious diabetes-related complications (Rother and

Harian, 2004). Blood sugar levels are monitored with a device like shown in (Figure 3), with a

small prick to a finger, a drop of blood is put into as test strip within the tester, therefore

calculating the diabetic individuals blood sugar level. Ideal blood sugar levels are anywhere from

80-120.

Figure 3. Blood sugar tester come in different sizes, shapes, and brands. Above is a newer model that after blood is tested sends the results to the individual’s insulin pump and informs it if more insulin is needed (photograph by author).

WHY IS A CURE FOR TYPE 1 DIABETES IMPORTANT

With all the necessary equipment to manage and live with type 1 diabetes why is there a

need for a cure? Finding a cure would not only eliminate type 1 diabetes, it would eliminate the

possibility of diabetes-related complications for that individual (Calafiore, 1997). Individuals

with type 1 diabetes are more susceptible to eye, nerve, kidney problems, and sometimes death if

not properly managed (Calafiore, 1997). Diabetes has no age limit, anyone can be type 1 or type

2. It is estimated that 7% of the United States population is diabetic (Funnell, 2007). With a cure

that percent could be lower or even lost, also leading to a lower number of diabetes-related

diseases.

There is much research on different possible cures, but this paper will focus on pancreas

transplantation and β-cell regeneration/replacement. Both of these methods have cured diabetes,

but many problems still arise with these forms of treatment (Bosi et al., 2001).

PANCREAS TRANSPLANTATION

Pancreas transplantation has been offered as a surgical cure for type 1 diabetes for many

years, but the requirements for receiving the treatment are strict (Gillespie, 2006; and White et

al., 2009). Diabetic individuals must be in severe condition to even be considered for

transplantation (Stevens et al., 2001). Poor metabolic control, hyperglycemia unawareness, and

failing renal function are all examples of what severe conditions would meet the requirements

(Robertson, 2004; and Steven et al., 2001). If transplantation takes place before these conditions

are present it is possible to reverse them (Manske, 1999), but if conditions are already present it

is likely that they are far to complicated to be treated (White et al., 2009).

Strict requirements are set due to a large lack of donor organs. In 1999 there were over

2000 individuals in need of a pancreas transplant with only half that number of available donor

organs (Stevens et al., 2001). Most donor organs are from an already deceased donor, but it is

possible to receive a graft from a live donor (White et al., 2009).

After being accepted and receiving a transplant the individual must undergo lifelong

immunosuppression to keep the organ from being rejected (Bosi et al., 2001; Calafiore, 1997;

and Gillespie, 2006), and many times depending on the immunosuppression used there is still

rejection of the organ from the body (Vendrame et al., 2010; and White et al., 2009). Rejection

rates are higher in younger recipients than older recipients, but older recipients have higher risks

for other complications after transplantation (White et al., 2009). Pancreas transplantation starts

with preparation of the donor pancreas as shown in (Figure 4).

Figure 4. this first photo shows a donor pancreas before reconstruction and the second image is of the reconstruction on the pancreas before transplantation using arteries from the donor (after White et al., 2009).

The donor pancreas is reconstructed using arteries from the donor and is surgically placed in the

pelvis of the recipient (White et al., 2009). Successful transplants though are not rejected, rid the

individual of type 1 diabetes by making insulin secretin normal, and make for normal blood

sugar levels (Elliott et al., 2001).

β -CELL REGENERATION/REPLACEMENT

With β-cell regeneration/replacement, it may be possible to stop the occurrence of type 1

diabetes altogether (Tomer et al., 2007). β-cell destruction is fast and goes unnoticed until the

time the individual is diagnosed as type 1 diabetic (Knip, 2011). In order to stop the occurrence

of diabetes altogether, scientists must first find a way to indicate when β-cell destruction is

happening. If able to indicate the start of destruction, it is now possible to restore insulin

production with β-cell replacement (Halban et al., 2001).

With less immunosuppression and no surgery, β-cell regeneration/replacement is a better

option than a pancreas transplantation (Robertson, 2004). β-cell regeneration/replacement is a

A

procedure in which β-cells are extracted from a donor pancreas and than inserted by injection

into the recipient (Ryan et al., 2002). A major problem with β-cell replacement is also the lack of

donors, unlike pancreas transplantation that only requires one donor organ, β-cell replacement

requires up to three donor organs to collect the right amount of β-cells needed to complete the

procedure (Bosi et al., 2001; Rickels et al., 2005; and Stevens et al., 2001). The reason for

requiring more than one donor organ is because of lack of proper isolation techniques (Calafiore,

1997; and Stevens et al., 2001). There are approximately 1 million β-cells in a single pancreas,

but due to improper isolation over half of those cells are lost (Calafiore, 1997; and Stevens et al.,

2001).

Long-term life of the donor cells within the body is also a problem, many times the

immune system is recognizing them as foreign and rejecting them from the body (Halban et al.,

2001 and Piemonti et al., 2013). Shutting down the immune systems attack on the cells will

make for a longer life of donor β-cells (Halban et al., 2001). An alternative to decreasing donor

use and avoiding the immune systems attack is the possibility of creating β-cell clones (Halban et

al., 2001). However, the β-cell is very complex and has the ability to change with insulin

alterations, which makes it difficult to replicate them (Halban et al., 2001). For every step

forward there seems to be a step back, but β-cell regeneration/replacement is a promising

possible cure, if obstacles are fixed.

DISCUSSION

The rapid destruction of the pancreatic β-cell leading to type 1 diabetes is unbelievably

complex (Funnell, 2007; Gillespie, 2006; and Rother and Harian, 2004). The most complicated

part about it all is the fact that the β-cell is not completely understood (Halban et al., 2001), the

β-cell is flexible and always responsive to change within the body (Halban et al., 2001). The

discovery of insulin was thought to cure type 1 diabetes and therefore restore β-cell function, but

it was soon found that insulin would only help manage type 1 diabetes, not cure it (Pickup and

Renard, 2008).

That is when the interest of pancreas transplantation took place and more recently β-cell

regeneration/replacement (Bosi et al., 2001; and Robertson, 2004). Success with pancreas

transplantation and type 1 diabetes led to the positive outlook on β-cell regeneration/replacement

(Robertson, 2004). Both types of treatment have a very different in route of procedure but have

the same outcome. The main issue of life-long immunosuppression with both pancreas

transplantation and β-cell regeneration/replacement, however, still remains (Bosi et al., 2001;

Calafiore, 1997; and Gillespie, 2006).

This articles purpose was to make the severity of type 1 diabetes known, give

understanding on insulin and its role with the diabetic individual, and give perspective on the

future of pancreas transplantation and β-cell regeneration/replacement as a cure for type 1

diabetes.

CONCLUSIONS

A. Type 1 diabetes is an autoimmune disorder that is caused by the destruction of pancreatic

insulin-producing cells, that can effect anyone at anytime.

B. Why is a cure for type 1 diabetes important?

C. What is insulin?

D. What is the ways insulin may be administered?

E. How do type 1 diabetes monitor their blood sugar levels?

F. What are the positives of pancreas transplantation as a type 1 diabetes cure?

G. What are the positives of β-cell regeneration/replacement as a type 1 diabetes cure?

H. What are the negatives to pancreas transplantation as a type 1 diabetes cure?

I. What are the negatives to β-cell regeneration/replacement as a type 1 diabetes cure?

J. Is pancreas transplantation or β-cell regeneration/replacement more successful as a type 1

diabetes cure?

ACKNOWLEDGMENTS

Special acknowledge for this article need to be made to Stephen Curry for allowing

photographs of his insulin pump and his tester. Also like to thank him for bringing interests

within this topic, his diagnosis with type 1 diabetes has drove future curiosity to look more

into the research for a type 1 diabetes cure. Would also like to acknowledge Dr. Graham

Baird and Professor Byron Straw, for all of their recommendations, critics, and teachings in

the Scientific Writing 291 class.

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